TY  - CONF
AU  - Nikolić, Ines
AU  - Petrović, Marija
AU  - Krupnik, Leondard
AU  - Randjelović, Danijela
AU  - Avaro, Jonathan
AU  - Neels, Antonia
AU  - Borchard, Gerrit
AU  - Jordan, Olivier
AU  - Đoković, Jelena
AU  - Savić, Snežana
PY  - 2023
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/6419
AB  - The aim of the presented research was to perform a thorough analysis of the selected nanosystem (nanoemulsion) focusing on size estimation and particle-protein interaction applying several state-of-the art techniques, highlighting important factors for a reliable analysis.
T1  - Sizing experiments and bio-nano interactions: method matters
UR  - https://hdl.handle.net/21.15107/rcub_cer_6419
ER  - 

@conference{
author = "Nikolić, Ines and Petrović, Marija and Krupnik, Leondard and Randjelović, Danijela and Avaro, Jonathan and Neels, Antonia and Borchard, Gerrit and Jordan, Olivier and Đoković, Jelena and Savić, Snežana",
year = "2023",
abstract = "The aim of the presented research was to perform a thorough analysis of the selected nanosystem (nanoemulsion) focusing on size estimation and particle-protein interaction applying several state-of-the art techniques, highlighting important factors for a reliable analysis.",
title = "Sizing experiments and bio-nano interactions: method matters",
url = "https://hdl.handle.net/21.15107/rcub_cer_6419"
}

Nikolić, I., Petrović, M., Krupnik, L., Randjelović, D., Avaro, J., Neels, A., Borchard, G., Jordan, O., Đoković, J.,& Savić, S.. (2023). Sizing experiments and bio-nano interactions: method matters. .
https://hdl.handle.net/21.15107/rcub_cer_6419

Nikolić I, Petrović M, Krupnik L, Randjelović D, Avaro J, Neels A, Borchard G, Jordan O, Đoković J, Savić S. Sizing experiments and bio-nano interactions: method matters. 2023;.
https://hdl.handle.net/21.15107/rcub_cer_6419 .

Nikolić, Ines, Petrović, Marija, Krupnik, Leondard, Randjelović, Danijela, Avaro, Jonathan, Neels, Antonia, Borchard, Gerrit, Jordan, Olivier, Đoković, Jelena, Savić, Snežana, "Sizing experiments and bio-nano interactions: method matters" (2023),
https://hdl.handle.net/21.15107/rcub_cer_6419 .

TY  - JOUR
AU  - Timotijević, Mirjana
AU  - Ilić, Tanja
AU  - Marković, Bojan
AU  - Randjelović, Danijela
AU  - Cekić, Nebojša
AU  - Nikolić, Ines
AU  - Savić, Snežana
AU  - Pantelić, Ivana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5258
AB  - Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization chal- lenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico- chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit® RS PO and hy- droxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm2 h), and even the pH of the sample with Eudragit® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study
VL  - 23
IS  - 11
DO  - 10.3390/ijms23116013
ER  - 

@article{
author = "Timotijević, Mirjana and Ilić, Tanja and Marković, Bojan and Randjelović, Danijela and Cekić, Nebojša and Nikolić, Ines and Savić, Snežana and Pantelić, Ivana",
year = "2022",
abstract = "Polymeric film-forming systems have emerged as an esthetically acceptable option for targeted, less frequent and controlled dermal drug delivery. However, their dynamic nature (rapid evaporation of solvents leading to the formation of thin films) presents a true characterization chal- lenge. In this study, we tested a tiered characterization approach, leading to more efficient definition of the quality target product profiles of film-forming systems. After assessing a number of physico- chemico-mechanical properties, thermal, spectroscopic and microscopic techniques were introduced. Final confirmation of betamethasone dipropionate-loaded FFS biopharmaceutical properties was sought via an in vitro skin permeation study. A number of applied characterization methods showed complementarity. The sample based on a combination of hydrophobic Eudragit® RS PO and hy- droxypropyl cellulose showed higher viscosity (47.17 ± 3.06 mPa·s) and film thickness, resulting in sustained skin permeation (permeation rate of 0.348 ± 0.157 ng/cm2 h), and even the pH of the sample with Eudragit® NE 30D, along with higher surface roughness and thermal analysis, implied its immediate delivery through the epidermal membrane. Therefore, this study revealed the utility of several methods able to refine the number of needed tests within the final product profile.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study",
volume = "23",
number = "11",
doi = "10.3390/ijms23116013"
}

Timotijević, M., Ilić, T., Marković, B., Randjelović, D., Cekić, N., Nikolić, I., Savić, S.,& Pantelić, I.. (2022). Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study. in International Journal of Molecular Sciences
MDPI., 23(11).
https://doi.org/10.3390/ijms23116013

Timotijević M, Ilić T, Marković B, Randjelović D, Cekić N, Nikolić I, Savić S, Pantelić I. Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study. in International Journal of Molecular Sciences. 2022;23(11).
doi:10.3390/ijms23116013 .

Timotijević, Mirjana, Ilić, Tanja, Marković, Bojan, Randjelović, Danijela, Cekić, Nebojša, Nikolić, Ines, Savić, Snežana, Pantelić, Ivana, "Coupling AFM, DSC and FT-IR towards Elucidation of Film-Forming Systems Transformation to Dermal Films: A Betamethasone Dipropionate Case Study" in International Journal of Molecular Sciences, 23, no. 11 (2022),
https://doi.org/10.3390/ijms23116013 . .

TY  - CONF
AU  - Mitrović, Jelena
AU  - Petković, Miloš
AU  - Randjelović, Danijela
AU  - Đoković, Jelena
AU  - Knutson, Daniel
AU  - Cook, James
AU  - Savić, Vladimir
AU  - Savić, Miroslav
AU  - Savić, Snežana
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5259
AB  - Poster presented at 13th World meeting on pharmaceutics, biopharmaceutics and pharmaceutical technology, 28-31 March 2022, Rotterdam, Netherlands
T1  - Physicochemical/structural investigation of lipid nanoparticles with high lecithin amounts loaded with patent protected pyrazoloquinolinone ligand DK-I-60-3
UR  - https://hdl.handle.net/21.15107/rcub_cer_5259
ER  - 

@conference{
author = "Mitrović, Jelena and Petković, Miloš and Randjelović, Danijela and Đoković, Jelena and Knutson, Daniel and Cook, James and Savić, Vladimir and Savić, Miroslav and Savić, Snežana",
year = "2022",
abstract = "Poster presented at 13th World meeting on pharmaceutics, biopharmaceutics and pharmaceutical technology, 28-31 March 2022, Rotterdam, Netherlands",
title = "Physicochemical/structural investigation of lipid nanoparticles with high lecithin amounts loaded with patent protected pyrazoloquinolinone ligand DK-I-60-3",
url = "https://hdl.handle.net/21.15107/rcub_cer_5259"
}

Mitrović, J., Petković, M., Randjelović, D., Đoković, J., Knutson, D., Cook, J., Savić, V., Savić, M.,& Savić, S.. (2022). Physicochemical/structural investigation of lipid nanoparticles with high lecithin amounts loaded with patent protected pyrazoloquinolinone ligand DK-I-60-3. .
https://hdl.handle.net/21.15107/rcub_cer_5259

Mitrović J, Petković M, Randjelović D, Đoković J, Knutson D, Cook J, Savić V, Savić M, Savić S. Physicochemical/structural investigation of lipid nanoparticles with high lecithin amounts loaded with patent protected pyrazoloquinolinone ligand DK-I-60-3. 2022;.
https://hdl.handle.net/21.15107/rcub_cer_5259 .

Mitrović, Jelena, Petković, Miloš, Randjelović, Danijela, Đoković, Jelena, Knutson, Daniel, Cook, James, Savić, Vladimir, Savić, Miroslav, Savić, Snežana, "Physicochemical/structural investigation of lipid nanoparticles with high lecithin amounts loaded with patent protected pyrazoloquinolinone ligand DK-I-60-3" (2022),
https://hdl.handle.net/21.15107/rcub_cer_5259 .

TY  - JOUR
AU  - Đoković, Jelena B.
AU  - Demisli, Sotiria
AU  - Savić, Sanela M.
AU  - Marković, Bojan D.
AU  - Cekić, Nebojša D.
AU  - Randjelović, Danijela
AU  - Mitrović, Jelena R.
AU  - Lunter, Dominique Jasmin
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Savić, Snežana D.
PY  - 2022
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/5375
AB  - A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsions.
PB  - Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)
T2  - Pharmaceutics
T1  - The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions
VL  - 14
IS  - 8
SP  - 1666
DO  - 10.3390/pharmaceutics14081666
ER  - 

@article{
author = "Đoković, Jelena B. and Demisli, Sotiria and Savić, Sanela M. and Marković, Bojan D. and Cekić, Nebojša D. and Randjelović, Danijela and Mitrović, Jelena R. and Lunter, Dominique Jasmin and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Savić, Snežana D.",
year = "2022",
abstract = "A nanotechnology-based approach to drug delivery presents one of the biggest trends in biomedical science that can provide increased active concentration, bioavailability, and safety compared to conventional drug-delivery systems. Nanoemulsions stand out amongst other nanocarriers for being biodegradable, biocompatible, and relatively easy to manufacture. For improved drug-delivery properties, longer circulation for the nanoemulsion droplets should be provided, to allow the active to reach the target site. One of the strategies used for this purpose is PEGylation. The aim of this research was assessing the impact of the oil phase selection, soybean or fish oil mixtures with medium chain triglycerides, on the physicochemical characteristics and injectability of curcumin-loaded PEGylated nanoemulsions. Electron paramagnetic resonance spectroscopy demonstrated the structural impact of the oil phase on the stabilizing layer of nanoemulsions, with a more pronounced stabilizing effect of curcumin observed in the fish oil nanoemulsion compared to the soybean oil one. The design of the experiment study, employed to simultaneously assess the impact of the oil phase, different PEGylated phospholipids and their concentrations, as well as the presence of curcumin, showed that not only the investigated factors alone, but also their interactions, had a significant influence on the critical quality attributes of the PEGylated nanoemulsions. Detailed physicochemical characterization of the NEs found all formulations were appropriate for parenteral administration and remained stable during two years of storage, with the preserved antioxidant activity demonstrated by DPPH and FRAP assays. In vitro release studies showed a more pronounced release of curcumin from the fish oil NEs compared to that from the soybean oil ones. The innovative in vitro injectability assessment, designed to mimic intravenous application, proved that all formulations tested in selected experimental setting could be employed in prospective in vivo studies. Overall, the current study shows the importance of oil phase selection when formulating PEGylated nanoemulsions.",
publisher = "Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)",
journal = "Pharmaceutics",
title = "The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions",
volume = "14",
number = "8",
pages = "1666",
doi = "10.3390/pharmaceutics14081666"
}

Đoković, J. B., Demisli, S., Savić, S. M., Marković, B. D., Cekić, N. D., Randjelović, D., Mitrović, J. R., Lunter, D. J., Papadimitriou, V., Xenakis, A.,& Savić, S. D.. (2022). The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions. in Pharmaceutics
Switzerland : Multidisciplinary Digital Publishing Institute (MDPI)., 14(8), 1666.
https://doi.org/10.3390/pharmaceutics14081666

Đoković JB, Demisli S, Savić SM, Marković BD, Cekić ND, Randjelović D, Mitrović JR, Lunter DJ, Papadimitriou V, Xenakis A, Savić SD. The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions. in Pharmaceutics. 2022;14(8):1666.
doi:10.3390/pharmaceutics14081666 .

Đoković, Jelena B., Demisli, Sotiria, Savić, Sanela M., Marković, Bojan D., Cekić, Nebojša D., Randjelović, Danijela, Mitrović, Jelena R., Lunter, Dominique Jasmin, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Savić, Snežana D., "The Impact of the Oil Phase Selection on Physicochemical Properties, Long-Term Stability, In Vitro Performance and Injectability of Curcumin-Loaded PEGylated Nanoemulsions" in Pharmaceutics, 14, no. 8 (2022):1666,
https://doi.org/10.3390/pharmaceutics14081666 . .

TY  - JOUR
AU  - Mitrović, Jelena
AU  - Divović-Matović, Branka
AU  - Knutson, Daniel E.
AU  - Ðoković, Jelena B.
AU  - Kremenović, Aleksandar
AU  - Dobričić, Vladimir
AU  - Randjelović, Danijela
AU  - Pantelić, Ivana
AU  - Cook, James
AU  - Savić, Miroslav M.
AU  - Savić, Snežana D.
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4791
AB  - Poor water solubility of new chemical entities is considered as one of the main obstacles in drug development, as it usually leads to low bioavailability after administration. To overcome these problems, the selection of the appropriate formulation technology needs to be based on the physicochemical properties of the drug and introduced in the early stages of drug research. One example of the new potential drug substance with poor solubility is DK-I-60-3, deuterated pyrazoloquinolinone, designed for the treatment of various neuropsychiatric disorders. In this research, based on preformulation studies, nanocrystal technology was chosen to improve the oral bioavailability of DK-I-60-3. Nanocrystal dispersions stabilized by sodium lauryl sulfate and polyvinylpyrrolidone were prepared by modified wet media milling technique, with the selection of appropriate process and formulation parameters. The nanoparticles characterization included particle size and zeta potential measurements, differential scanning calorimetry, X-ray powder diffraction, dissolution and solubility study, and in vivo pharmacokinetic experiments. Developed formulations had small uniform particle sizes and were stable for three months. Nanonization caused decreased crystallite size and induced crystal defects formation, as well as a DK-I-60-3 solubility increase. Furthermore, after oral administration of the developed formulations in rats, two to three-fold bioavailability enhancement was observed in plasma and investigated organs, including the brain.
PB  - MDPI
T2  - Pharmaceutics
T1  - Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach
VL  - 13
IS  - 8
SP  - 1188
DO  - 10.3390/pharmaceutics13081188
ER  - 

@article{
author = "Mitrović, Jelena and Divović-Matović, Branka and Knutson, Daniel E. and Ðoković, Jelena B. and Kremenović, Aleksandar and Dobričić, Vladimir and Randjelović, Danijela and Pantelić, Ivana and Cook, James and Savić, Miroslav M. and Savić, Snežana D.",
year = "2021",
abstract = "Poor water solubility of new chemical entities is considered as one of the main obstacles in drug development, as it usually leads to low bioavailability after administration. To overcome these problems, the selection of the appropriate formulation technology needs to be based on the physicochemical properties of the drug and introduced in the early stages of drug research. One example of the new potential drug substance with poor solubility is DK-I-60-3, deuterated pyrazoloquinolinone, designed for the treatment of various neuropsychiatric disorders. In this research, based on preformulation studies, nanocrystal technology was chosen to improve the oral bioavailability of DK-I-60-3. Nanocrystal dispersions stabilized by sodium lauryl sulfate and polyvinylpyrrolidone were prepared by modified wet media milling technique, with the selection of appropriate process and formulation parameters. The nanoparticles characterization included particle size and zeta potential measurements, differential scanning calorimetry, X-ray powder diffraction, dissolution and solubility study, and in vivo pharmacokinetic experiments. Developed formulations had small uniform particle sizes and were stable for three months. Nanonization caused decreased crystallite size and induced crystal defects formation, as well as a DK-I-60-3 solubility increase. Furthermore, after oral administration of the developed formulations in rats, two to three-fold bioavailability enhancement was observed in plasma and investigated organs, including the brain.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach",
volume = "13",
number = "8",
pages = "1188",
doi = "10.3390/pharmaceutics13081188"
}

Mitrović, J., Divović-Matović, B., Knutson, D. E., Ðoković, J. B., Kremenović, A., Dobričić, V., Randjelović, D., Pantelić, I., Cook, J., Savić, M. M.,& Savić, S. D.. (2021). Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach. in Pharmaceutics
MDPI., 13(8), 1188.
https://doi.org/10.3390/pharmaceutics13081188

Mitrović J, Divović-Matović B, Knutson DE, Ðoković JB, Kremenović A, Dobričić V, Randjelović D, Pantelić I, Cook J, Savić MM, Savić SD. Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach. in Pharmaceutics. 2021;13(8):1188.
doi:10.3390/pharmaceutics13081188 .

Mitrović, Jelena, Divović-Matović, Branka, Knutson, Daniel E., Ðoković, Jelena B., Kremenović, Aleksandar, Dobričić, Vladimir, Randjelović, Danijela, Pantelić, Ivana, Cook, James, Savić, Miroslav M., Savić, Snežana D., "Overcoming the low oral bioavailability of deuterated pyrazoloquinolinone ligand dk-i-60-3 by nanonization: A knowledge-based approach" in Pharmaceutics, 13, no. 8 (2021):1188,
https://doi.org/10.3390/pharmaceutics13081188 . .

TY  - JOUR
AU  - Gledović, Ana
AU  - Janošević Ležaić, Aleksandra
AU  - Nikolić, Ines
AU  - Tasić-Kostov, Marija Z.
AU  - Antić-Stanković, Jelena
AU  - Krstonošić, Veljko S.
AU  - Randjelović, Danijela
AU  - Božić, Dragana
AU  - Ilić, Dušan
AU  - Tamburić, Slobodanka D.
AU  - Savić, Snežana
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4243
AB  - This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions
based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO
and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions
were obtained via phase inversion composition (PIC) method at room temperature by dilution of
microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic,
rheological and differential scanning calorimetry (DSC) investigations. The results have shown that
the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from
red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet
size (Z-ave: 50 to 70 nm, PDI value _ 0.1). The highest antioxidant activity (~92% inhibition of the
DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic
antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased
the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal
human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles
and significant improvement in skin hydration during 2 h after application for all nanoemulsions.
Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red
raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin
protection and hydration.
PB  - MDPI
T2  - Nanomaterials
T1  - Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance
VL  - 11
IS  - 1
SP  - 1
EP  - 21
DO  - 10.3390/nano11010217
ER  - 

@article{
author = "Gledović, Ana and Janošević Ležaić, Aleksandra and Nikolić, Ines and Tasić-Kostov, Marija Z. and Antić-Stanković, Jelena and Krstonošić, Veljko S. and Randjelović, Danijela and Božić, Dragana and Ilić, Dušan and Tamburić, Slobodanka D. and Savić, Snežana",
year = "2021",
abstract = "This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions
based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO
and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions
were obtained via phase inversion composition (PIC) method at room temperature by dilution of
microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic,
rheological and differential scanning calorimetry (DSC) investigations. The results have shown that
the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from
red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet
size (Z-ave: 50 to 70 nm, PDI value _ 0.1). The highest antioxidant activity (~92% inhibition of the
DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic
antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased
the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal
human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles
and significant improvement in skin hydration during 2 h after application for all nanoemulsions.
Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red
raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin
protection and hydration.",
publisher = "MDPI",
journal = "Nanomaterials",
title = "Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance",
volume = "11",
number = "1",
pages = "1-21",
doi = "10.3390/nano11010217"
}

Gledović, A., Janošević Ležaić, A., Nikolić, I., Tasić-Kostov, M. Z., Antić-Stanković, J., Krstonošić, V. S., Randjelović, D., Božić, D., Ilić, D., Tamburić, S. D.,& Savić, S.. (2021). Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance. in Nanomaterials
MDPI., 11(1), 1-21.
https://doi.org/10.3390/nano11010217

Gledović A, Janošević Ležaić A, Nikolić I, Tasić-Kostov MZ, Antić-Stanković J, Krstonošić VS, Randjelović D, Božić D, Ilić D, Tamburić SD, Savić S. Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance. in Nanomaterials. 2021;11(1):1-21.
doi:10.3390/nano11010217 .

Gledović, Ana, Janošević Ležaić, Aleksandra, Nikolić, Ines, Tasić-Kostov, Marija Z., Antić-Stanković, Jelena, Krstonošić, Veljko S., Randjelović, Danijela, Božić, Dragana, Ilić, Dušan, Tamburić, Slobodanka D., Savić, Snežana, "Polyglycerol Ester-Based Low Energy Nanoemulsions with Red Raspberry Seed Oil and Fruit Extracts: Formulation Development toward Effective In Vitro/In Vivo Bioperformance" in Nanomaterials, 11, no. 1 (2021):1-21,
https://doi.org/10.3390/nano11010217 . .

TY  - JOUR
AU  - Ðoković, Jelena B.
AU  - Savić, Sanela M.
AU  - Mitrović, Jelena R.
AU  - Nikolić, Ines
AU  - Marković, Bojan D.
AU  - Randjelović, Danijela
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Cekić, Nebojša D.
AU  - Stevanović, Vladimir
AU  - Batinić, Bojan
AU  - Aranđelović, Jovana
AU  - Savić, Miroslav M.
AU  - Savić, Snežana D.
PY  - 2021
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4822
AB  - The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.
PB  - MDPI
T2  - International Journal of Molecular Sciences
T1  - Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats
VL  - 22
IS  - 15
IS  - 7991
DO  - 10.3390/ijms22157991
ER  - 

@article{
author = "Ðoković, Jelena B. and Savić, Sanela M. and Mitrović, Jelena R. and Nikolić, Ines and Marković, Bojan D. and Randjelović, Danijela and Antić-Stanković, Jelena and Božić, Dragana and Cekić, Nebojša D. and Stevanović, Vladimir and Batinić, Bojan and Aranđelović, Jovana and Savić, Miroslav M. and Savić, Snežana D.",
year = "2021",
abstract = "The current study describes the experimental design guided development of PEGylated nanoemulsions as parenteral delivery systems for curcumin, a powerful antioxidant, as well as the evaluation of their physicochemical characteristics and antioxidant activity during the two years of storage. Experimental design setup helped development of nanoemulsion templates with critical quality attributes in line with parenteral application route. Curcumin-loaded nanoemulsions showed mean droplet size about 105 nm, polydispersity index <0.15, zeta potential of −40 mV, and acceptable osmolality of about 550 mOsm/kg. After two years of storage at room temperature, all formulations remained stable. Moreover, antioxidant activity remained intact, as demonstrated by DPPH (IC50 values 0.078–0.075 mg/mL after two years) and FRAPS assays. In vitro release testing proved that PEGylated phospholipids slowed down the curcumin release from nanoemulsions. The nanoemulsion carrier has been proven safe by the MTT test conducted with MRC-5 cell line, and effective on LS cell line. Results from the pharmacokinetic pilot study implied the PEGylated nanoemulsions improved plasma residence of curcumin 20 min after intravenous administration, compared to the non-PEGylated nanoemulsion (two-fold higher) or curcumin solution (three-fold higher). Overall, conclusion suggests that developed PEGylated nanoemulsions present an acceptable delivery system for parenteral administration of curcumin, being effective in preserving its stability and antioxidant capacity at the level highly comparable to the initial findings.",
publisher = "MDPI",
journal = "International Journal of Molecular Sciences",
title = "Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats",
volume = "22",
number = "15, 7991",
doi = "10.3390/ijms22157991"
}

Ðoković, J. B., Savić, S. M., Mitrović, J. R., Nikolić, I., Marković, B. D., Randjelović, D., Antić-Stanković, J., Božić, D., Cekić, N. D., Stevanović, V., Batinić, B., Aranđelović, J., Savić, M. M.,& Savić, S. D.. (2021). Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats. in International Journal of Molecular Sciences
MDPI., 22(15).
https://doi.org/10.3390/ijms22157991

Ðoković JB, Savić SM, Mitrović JR, Nikolić I, Marković BD, Randjelović D, Antić-Stanković J, Božić D, Cekić ND, Stevanović V, Batinić B, Aranđelović J, Savić MM, Savić SD. Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats. in International Journal of Molecular Sciences. 2021;22(15).
doi:10.3390/ijms22157991 .

Ðoković, Jelena B., Savić, Sanela M., Mitrović, Jelena R., Nikolić, Ines, Marković, Bojan D., Randjelović, Danijela, Antić-Stanković, Jelena, Božić, Dragana, Cekić, Nebojša D., Stevanović, Vladimir, Batinić, Bojan, Aranđelović, Jovana, Savić, Miroslav M., Savić, Snežana D., "Curcumin loaded pegylated nanoemulsions designed for maintained antioxidant effects and improved bioavailability: A pilot study on rats" in International Journal of Molecular Sciences, 22, no. 15 (2021),
https://doi.org/10.3390/ijms22157991 . .

TY  - JOUR
AU  - Nikolić, Ines
AU  - Antić-Stanković, Jelena
AU  - Božić, Dragana
AU  - Randjelović, Danijela
AU  - Marković, Bojan D.
AU  - Lunter, Dominique Jasmin
AU  - Kremenović, Aleksandar
AU  - Savić, Miroslav M.
AU  - Savić, Snežana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3711
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3720
AB  - As the number of poorly soluble drugs is increasing, nanocrystals have become very interesting due to wide range of application possibilities. Curcuminwas used as a model active ingredient in this work. Even though it has many proven positive effects, due to its physicochemical issues, its possibilities have not been fully exploited. The goal of this work was to select optimal conditions for a top-down method for curcumin nanosuspension production, and to perform their comprehensive characterization applying complementary methodologies: dynamic light scattering, polarization and atomic force microscopy, thermal analysis, X-ray powder diffraction, antioxidant activity evaluation, release kinetics assessment, and screening of potential biological effects applying cell viability assays on normal human lung fibroblasts, human melanoma and human adenomacarcinoma cells. After 30 min of milling, nanosuspensions stabilized by polysorbate 80 and by its combinations with sucrose palmitate showed good stability, while curcumin crystal structure was unaltered. Obtained nanocrystals were well defined, with average diameter 120-170 nm and PDI of about 0.25, zeta potential was below -30 mV and pH~5 for all formulations. Nanodispersions exhibited high antioxidant potential and improved dissolution rate compared to the corresponding coarse dispersions. Although curcumin nanodispersions exhibited significant antiproliferative effect to each cancer cell line, the highest effect was towards adenocarcinoma cells.
PB  - Walter de Gruyter GmbH
T2  - Reviews on Advanced Materials Science
T1  - Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals
VL  - 59
IS  - 1
SP  - 406
EP  - 424
DO  - 10.1515/rams-2020-0043
ER  - 

@article{
author = "Nikolić, Ines and Antić-Stanković, Jelena and Božić, Dragana and Randjelović, Danijela and Marković, Bojan D. and Lunter, Dominique Jasmin and Kremenović, Aleksandar and Savić, Miroslav M. and Savić, Snežana",
year = "2020",
abstract = "As the number of poorly soluble drugs is increasing, nanocrystals have become very interesting due to wide range of application possibilities. Curcuminwas used as a model active ingredient in this work. Even though it has many proven positive effects, due to its physicochemical issues, its possibilities have not been fully exploited. The goal of this work was to select optimal conditions for a top-down method for curcumin nanosuspension production, and to perform their comprehensive characterization applying complementary methodologies: dynamic light scattering, polarization and atomic force microscopy, thermal analysis, X-ray powder diffraction, antioxidant activity evaluation, release kinetics assessment, and screening of potential biological effects applying cell viability assays on normal human lung fibroblasts, human melanoma and human adenomacarcinoma cells. After 30 min of milling, nanosuspensions stabilized by polysorbate 80 and by its combinations with sucrose palmitate showed good stability, while curcumin crystal structure was unaltered. Obtained nanocrystals were well defined, with average diameter 120-170 nm and PDI of about 0.25, zeta potential was below -30 mV and pH~5 for all formulations. Nanodispersions exhibited high antioxidant potential and improved dissolution rate compared to the corresponding coarse dispersions. Although curcumin nanodispersions exhibited significant antiproliferative effect to each cancer cell line, the highest effect was towards adenocarcinoma cells.",
publisher = "Walter de Gruyter GmbH",
journal = "Reviews on Advanced Materials Science",
title = "Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals",
volume = "59",
number = "1",
pages = "406-424",
doi = "10.1515/rams-2020-0043"
}

Nikolić, I., Antić-Stanković, J., Božić, D., Randjelović, D., Marković, B. D., Lunter, D. J., Kremenović, A., Savić, M. M.,& Savić, S.. (2020). Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals. in Reviews on Advanced Materials Science
Walter de Gruyter GmbH., 59(1), 406-424.
https://doi.org/10.1515/rams-2020-0043

Nikolić I, Antić-Stanković J, Božić D, Randjelović D, Marković BD, Lunter DJ, Kremenović A, Savić MM, Savić S. Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals. in Reviews on Advanced Materials Science. 2020;59(1):406-424.
doi:10.1515/rams-2020-0043 .

Nikolić, Ines, Antić-Stanković, Jelena, Božić, Dragana, Randjelović, Danijela, Marković, Bojan D., Lunter, Dominique Jasmin, Kremenović, Aleksandar, Savić, Miroslav M., Savić, Snežana, "Curcumin Nanonization Using An Alternative Small-Scale Production Unit: Selection of Proper Stabilizer Applying Basic Physicochemical Consideration and Biological Activity Assessment of Nanocrystals" in Reviews on Advanced Materials Science, 59, no. 1 (2020):406-424,
https://doi.org/10.1515/rams-2020-0043 . .

TY  - JOUR
AU  - Gledović, Ana
AU  - Janošević Ležaić, Aleksandra
AU  - Krstonosic, Veljko
AU  - Djokovic, Jelena
AU  - Nikolić, Ines
AU  - Bajuk-Bogdanovic, Danica
AU  - Antić Stanković, Jelena
AU  - Randjelović, Danijela
AU  - Savić, Sanela M.
AU  - Filipović, Mila
AU  - Tamburic, Slobodanka
AU  - Savić, Snežana D.
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3516
AB  - Considering a growing demand for medicinal/cosmetic products with natural actives, this study focuses on the low-energy nanoemulsions (LE-NEs) prepared via the Phase inversion composition (PIC) method at room temperature as potential carriers for natural oil. Four different red raspberry seed oils (ROs) were tested, as follows: cold-pressed vs. CO2-extracted, organic vs. non-organic, refined vs. unrefined. The oil phase was optimized with Tocopheryl acetate and Isostearyl isostearate, while water phase was adjusted with either glycerol or an antioxidant hydro-glycolic extract. This study has used a combined approach to formulation development, employing both conventional methods (pseudo-ternary phase diagram − PTPD, electrical conductivity, particle size measurements, microscopical analysis, and rheological measurements) and the methods novel to this area, such as textural analysis and Raman spectroscopy. Raman spectroscopy has detected fine differences in chemical composition among ROs, and it detected the interactions within nanoemulsions. It was shown that the cold-pressed, unrefined, organic grade oil (RO2) with 6.62% saturated fatty acids and 92.25% unsaturated fatty acids, was optimal for the LE-NEs. Textural analysis confirmed the existence of cubic gel-like phase as a crucial step in the formation of stable RO2-loaded LE-NEs, with droplets in the narrow nano-range (125 to 135 nm; PDI ≤ 0.1). The DPPH test in methanol and ABTS in aqueous medium have revealed a synergistic free radical scavenging effect between lipophilic and hydrophilic antioxidants in LE-NEs. The nanoemulsion carrier has improved the biological effect of raw materials on HeLa cervical adenocarcinoma cells, while exhibiting good safety profile, as confirmed on MRC-5 normal human lung fibroblasts. Overall, this study has shown that low-energy nanoemulsions present very promising carriers for topical delivery of natural bioactives. Raman spectroscopy and textural analysis have proven to be a useful addition to the arsenal of methods used in the formulation and characterization of nanoemulsion systems.
PB  - Public Library of Science (PLoS)
T2  - PLOS ONE
T1  - Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity
VL  - 15
IS  - 4
SP  - e0230993
DO  - 10.1371/journal.pone.0230993
ER  - 

@article{
author = "Gledović, Ana and Janošević Ležaić, Aleksandra and Krstonosic, Veljko and Djokovic, Jelena and Nikolić, Ines and Bajuk-Bogdanovic, Danica and Antić Stanković, Jelena and Randjelović, Danijela and Savić, Sanela M. and Filipović, Mila and Tamburic, Slobodanka and Savić, Snežana D.",
year = "2020",
abstract = "Considering a growing demand for medicinal/cosmetic products with natural actives, this study focuses on the low-energy nanoemulsions (LE-NEs) prepared via the Phase inversion composition (PIC) method at room temperature as potential carriers for natural oil. Four different red raspberry seed oils (ROs) were tested, as follows: cold-pressed vs. CO2-extracted, organic vs. non-organic, refined vs. unrefined. The oil phase was optimized with Tocopheryl acetate and Isostearyl isostearate, while water phase was adjusted with either glycerol or an antioxidant hydro-glycolic extract. This study has used a combined approach to formulation development, employing both conventional methods (pseudo-ternary phase diagram − PTPD, electrical conductivity, particle size measurements, microscopical analysis, and rheological measurements) and the methods novel to this area, such as textural analysis and Raman spectroscopy. Raman spectroscopy has detected fine differences in chemical composition among ROs, and it detected the interactions within nanoemulsions. It was shown that the cold-pressed, unrefined, organic grade oil (RO2) with 6.62% saturated fatty acids and 92.25% unsaturated fatty acids, was optimal for the LE-NEs. Textural analysis confirmed the existence of cubic gel-like phase as a crucial step in the formation of stable RO2-loaded LE-NEs, with droplets in the narrow nano-range (125 to 135 nm; PDI ≤ 0.1). The DPPH test in methanol and ABTS in aqueous medium have revealed a synergistic free radical scavenging effect between lipophilic and hydrophilic antioxidants in LE-NEs. The nanoemulsion carrier has improved the biological effect of raw materials on HeLa cervical adenocarcinoma cells, while exhibiting good safety profile, as confirmed on MRC-5 normal human lung fibroblasts. Overall, this study has shown that low-energy nanoemulsions present very promising carriers for topical delivery of natural bioactives. Raman spectroscopy and textural analysis have proven to be a useful addition to the arsenal of methods used in the formulation and characterization of nanoemulsion systems.",
publisher = "Public Library of Science (PLoS)",
journal = "PLOS ONE",
title = "Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity",
volume = "15",
number = "4",
pages = "e0230993",
doi = "10.1371/journal.pone.0230993"
}

Gledović, A., Janošević Ležaić, A., Krstonosic, V., Djokovic, J., Nikolić, I., Bajuk-Bogdanovic, D., Antić Stanković, J., Randjelović, D., Savić, S. M., Filipović, M., Tamburic, S.,& Savić, S. D.. (2020). Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity. in PLOS ONE
Public Library of Science (PLoS)., 15(4), e0230993.
https://doi.org/10.1371/journal.pone.0230993

Gledović A, Janošević Ležaić A, Krstonosic V, Djokovic J, Nikolić I, Bajuk-Bogdanovic D, Antić Stanković J, Randjelović D, Savić SM, Filipović M, Tamburic S, Savić SD. Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity. in PLOS ONE. 2020;15(4):e0230993.
doi:10.1371/journal.pone.0230993 .

Gledović, Ana, Janošević Ležaić, Aleksandra, Krstonosic, Veljko, Djokovic, Jelena, Nikolić, Ines, Bajuk-Bogdanovic, Danica, Antić Stanković, Jelena, Randjelović, Danijela, Savić, Sanela M., Filipović, Mila, Tamburic, Slobodanka, Savić, Snežana D., "Low-energy nanoemulsions as carriers for red raspberry seed oil: Formulation approach based on Raman spectroscopy and textural analysis, physicochemical properties, stability and in vitro antioxidant/ biological activity" in PLOS ONE, 15, no. 4 (2020):e0230993,
https://doi.org/10.1371/journal.pone.0230993 . .

TY  - JOUR
AU  - Jurišić Dukovski, Bisera
AU  - Juretić, Marina
AU  - Bračko, Danka
AU  - Randjelović, Danijela
AU  - Savić, Snežana
AU  - Crespo Moral, Mario
AU  - Diebold, Yolanda
AU  - Filipović-Grčić, Jelena
AU  - Pepić, Ivan
AU  - Lovrić, Jasmina
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4011
AB  - Abstract: Inflammation plays a key role in dry eye disease (DED)
affecting millions of people worldwide. Non-steroidal anti-inflammatory
drugs (NSAIDs) can be used topically to act on the inflammatory component
of DED, but their limited aqueous solubility raises formulation issues.
The aim of this study was development and optimization of functional
cationic nanoemulsions (NEs) for DED treatment, as a formulation approach
to circumvent solubility problems, prolong drug residence at the ocular
surface and stabilize the tear film. Ibuprofen was employed as the model
NSAID, chitosan as the cationic agent, and lecithin as the anionic
surfactant enabling chitosan incorporation. Moreover, lecithin is a
mixture of phospholipids including phosphatidylcholine and
phosphatidylethanolamine, two constituents of the natural tear film
important for its stability. NEs were characterized in terms of droplet
size, polydispersity index, zeta-potential, pH, viscosity, osmolarity,
surface tension, entrapment efficiency, stability, sterilizability and in
vitro release. NEs mucoadhesive properties were tested rheologically
after mixing with mucin dispersion. Biocompatibility was assessed
employing 3D HCE-T cell-based model and ex vivo model using porcine
corneas. The results of our study pointed out the NE formulation with
0.05 % (w/w) chitosan as the lead formulation with physicochemical
properties adequate for ophthalmic application, mucoadhesive character
and excellent biocompatibility.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment
VL  - 576
SP  - 118979
DO  - 10.1016/j.ijpharm.2019.118979
ER  - 

@article{
author = "Jurišić Dukovski, Bisera and Juretić, Marina and Bračko, Danka and Randjelović, Danijela and Savić, Snežana and Crespo Moral, Mario and Diebold, Yolanda and Filipović-Grčić, Jelena and Pepić, Ivan and Lovrić, Jasmina",
year = "2020",
abstract = "Abstract: Inflammation plays a key role in dry eye disease (DED)
affecting millions of people worldwide. Non-steroidal anti-inflammatory
drugs (NSAIDs) can be used topically to act on the inflammatory component
of DED, but their limited aqueous solubility raises formulation issues.
The aim of this study was development and optimization of functional
cationic nanoemulsions (NEs) for DED treatment, as a formulation approach
to circumvent solubility problems, prolong drug residence at the ocular
surface and stabilize the tear film. Ibuprofen was employed as the model
NSAID, chitosan as the cationic agent, and lecithin as the anionic
surfactant enabling chitosan incorporation. Moreover, lecithin is a
mixture of phospholipids including phosphatidylcholine and
phosphatidylethanolamine, two constituents of the natural tear film
important for its stability. NEs were characterized in terms of droplet
size, polydispersity index, zeta-potential, pH, viscosity, osmolarity,
surface tension, entrapment efficiency, stability, sterilizability and in
vitro release. NEs mucoadhesive properties were tested rheologically
after mixing with mucin dispersion. Biocompatibility was assessed
employing 3D HCE-T cell-based model and ex vivo model using porcine
corneas. The results of our study pointed out the NE formulation with
0.05 % (w/w) chitosan as the lead formulation with physicochemical
properties adequate for ophthalmic application, mucoadhesive character
and excellent biocompatibility.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment",
volume = "576",
pages = "118979",
doi = "10.1016/j.ijpharm.2019.118979"
}

Jurišić Dukovski, B., Juretić, M., Bračko, D., Randjelović, D., Savić, S., Crespo Moral, M., Diebold, Y., Filipović-Grčić, J., Pepić, I.,& Lovrić, J.. (2020). Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment. in International Journal of Pharmaceutics
Elsevier., 576, 118979.
https://doi.org/10.1016/j.ijpharm.2019.118979

Jurišić Dukovski B, Juretić M, Bračko D, Randjelović D, Savić S, Crespo Moral M, Diebold Y, Filipović-Grčić J, Pepić I, Lovrić J. Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment. in International Journal of Pharmaceutics. 2020;576:118979.
doi:10.1016/j.ijpharm.2019.118979 .

Jurišić Dukovski, Bisera, Juretić, Marina, Bračko, Danka, Randjelović, Danijela, Savić, Snežana, Crespo Moral, Mario, Diebold, Yolanda, Filipović-Grčić, Jelena, Pepić, Ivan, Lovrić, Jasmina, "Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment" in International Journal of Pharmaceutics, 576 (2020):118979,
https://doi.org/10.1016/j.ijpharm.2019.118979 . .

TY  - JOUR
AU  - Jurišić Dukovski, Bisera
AU  - Juretić, Marina
AU  - Bračko, Danka
AU  - Randjelović, Danijela
AU  - Savić, Snežana
AU  - Crespo Moral, Mario
AU  - Diebold, Yolanda
AU  - Filipović-Grčić, Jelena
AU  - Pepić, Ivan
AU  - Lovrić, Jasmina
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4012
AB  - Abstract: Inflammation plays a key role in dry eye disease (DED)affecting millions of people worldwide. Non-steroidal anti-inflammatorydrugs (NSAIDs) can be used topically to act on the inflammatory componentof DED, but their limited aqueous solubility raises formulation issues.The aim of this study was development and optimization of functionalcationic nanoemulsions (NEs) for DED treatment, as a formulation approachto circumvent solubility problems, prolong drug residence at the ocularsurface and stabilize the tear film. Ibuprofen was employed as the modelNSAID, chitosan as the cationic agent, and lecithin as the anionicsurfactant enabling chitosan incorporation. Moreover, lecithin is amixture of phospholipids including phosphatidylcholine andphosphatidylethanolamine, two constituents of the natural tear filmimportant for its stability. NEs were characterized in terms of dropletsize, polydispersity index, zeta-potential, pH, viscosity, osmolarity,surface tension, entrapment efficiency, stability, sterilizability and invitro release. NEs mucoadhesive properties were tested rheologicallyafter mixing with mucin dispersion. Biocompatibility was assessedemploying 3D HCE-T cell-based model and ex vivo model using porcinecorneas. The results of our study pointed out the NE formulation with0.05 % (w/w) chitosan as the lead formulation with physicochemicalproperties adequate for ophthalmic application, mucoadhesive characterand excellent biocompatibility.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment
VL  - 576
SP  - 118979
DO  - 10.1016/j.ijpharm.2019.118979
ER  - 

@article{
author = "Jurišić Dukovski, Bisera and Juretić, Marina and Bračko, Danka and Randjelović, Danijela and Savić, Snežana and Crespo Moral, Mario and Diebold, Yolanda and Filipović-Grčić, Jelena and Pepić, Ivan and Lovrić, Jasmina",
year = "2020",
abstract = "Abstract: Inflammation plays a key role in dry eye disease (DED)affecting millions of people worldwide. Non-steroidal anti-inflammatorydrugs (NSAIDs) can be used topically to act on the inflammatory componentof DED, but their limited aqueous solubility raises formulation issues.The aim of this study was development and optimization of functionalcationic nanoemulsions (NEs) for DED treatment, as a formulation approachto circumvent solubility problems, prolong drug residence at the ocularsurface and stabilize the tear film. Ibuprofen was employed as the modelNSAID, chitosan as the cationic agent, and lecithin as the anionicsurfactant enabling chitosan incorporation. Moreover, lecithin is amixture of phospholipids including phosphatidylcholine andphosphatidylethanolamine, two constituents of the natural tear filmimportant for its stability. NEs were characterized in terms of dropletsize, polydispersity index, zeta-potential, pH, viscosity, osmolarity,surface tension, entrapment efficiency, stability, sterilizability and invitro release. NEs mucoadhesive properties were tested rheologicallyafter mixing with mucin dispersion. Biocompatibility was assessedemploying 3D HCE-T cell-based model and ex vivo model using porcinecorneas. The results of our study pointed out the NE formulation with0.05 % (w/w) chitosan as the lead formulation with physicochemicalproperties adequate for ophthalmic application, mucoadhesive characterand excellent biocompatibility.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment",
volume = "576",
pages = "118979",
doi = "10.1016/j.ijpharm.2019.118979"
}

Jurišić Dukovski, B., Juretić, M., Bračko, D., Randjelović, D., Savić, S., Crespo Moral, M., Diebold, Y., Filipović-Grčić, J., Pepić, I.,& Lovrić, J.. (2020). Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment. in International Journal of Pharmaceutics
Elsevier., 576, 118979.
https://doi.org/10.1016/j.ijpharm.2019.118979

Jurišić Dukovski B, Juretić M, Bračko D, Randjelović D, Savić S, Crespo Moral M, Diebold Y, Filipović-Grčić J, Pepić I, Lovrić J. Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment. in International Journal of Pharmaceutics. 2020;576:118979.
doi:10.1016/j.ijpharm.2019.118979 .

Jurišić Dukovski, Bisera, Juretić, Marina, Bračko, Danka, Randjelović, Danijela, Savić, Snežana, Crespo Moral, Mario, Diebold, Yolanda, Filipović-Grčić, Jelena, Pepić, Ivan, Lovrić, Jasmina, "Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment" in International Journal of Pharmaceutics, 576 (2020):118979,
https://doi.org/10.1016/j.ijpharm.2019.118979 . .

TY  - JOUR
AU  - Mitrović, Jelena
AU  - Divović, Branka
AU  - Knutson, Daniel
AU  - Đoković, Jelena
AU  - Vulić, Predrag
AU  - Randjelović, Danijela
AU  - Dobričić, Vladimir
AU  - Čalija, Bojan
AU  - Cook, James
AU  - Savić, Miroslav M.
AU  - Savić, Snežana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3714
AB  - DK-I-56–1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one), a recently developed deuterated pyrazoloquinolinone, has been recognized as a lead candidate for treatment of various neuropsychiatric disorders. During preclinical investigation of poorly water-soluble compounds such as DK-I-56–1, the application of nanotechnology could be advantageous due to improved safety and possibly increased bioavailability of nanosized formulation. DK-I-56–1 nanosuspensions stabilized by polysorbate 80, alone or in combination with poloxamers 188 i.e. 407 or D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared using a small-scale media milling device. With particle size 208.7–250.6 nm and polydispersity index <0.250, selected nanodiseprsions were stable for three weeks. Pharmacokinetic and biodistribution studies following intraperitoneal administration of three types of formulation in mice indicated high plasma DK-I-56–1 levels after solution (10,228.6 ± 1037.2 ngh/ml) and nanosuspension (6770.4 ± 770.7 ngh/ml) but not suspension administration (966.0 ± 58.1 ngh/ml). However, distribution of DK-I-56–1 after solution was heavily influenced by its composition, and brain availability of nanosuspension was superior to that of solution formulation. In spontaneous locomotor activity test, the expected hyperlocomotor effect was observed after nanosuspension administration, without compromising impact of the vehicle/excipients used. Therefore, nanonization of drug compound assembled with proper selection of stabilizers may seemingly contribute further thorough testing of DK-I-56–1 preclinical efficacy.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Science
T1  - Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance
VL  - 152
SP  - 105432
DO  - 10.1016/j.ejps.2020.105432
ER  - 

@article{
author = "Mitrović, Jelena and Divović, Branka and Knutson, Daniel and Đoković, Jelena and Vulić, Predrag and Randjelović, Danijela and Dobričić, Vladimir and Čalija, Bojan and Cook, James and Savić, Miroslav M. and Savić, Snežana",
year = "2020",
abstract = "DK-I-56–1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one), a recently developed deuterated pyrazoloquinolinone, has been recognized as a lead candidate for treatment of various neuropsychiatric disorders. During preclinical investigation of poorly water-soluble compounds such as DK-I-56–1, the application of nanotechnology could be advantageous due to improved safety and possibly increased bioavailability of nanosized formulation. DK-I-56–1 nanosuspensions stabilized by polysorbate 80, alone or in combination with poloxamers 188 i.e. 407 or D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared using a small-scale media milling device. With particle size 208.7–250.6 nm and polydispersity index <0.250, selected nanodiseprsions were stable for three weeks. Pharmacokinetic and biodistribution studies following intraperitoneal administration of three types of formulation in mice indicated high plasma DK-I-56–1 levels after solution (10,228.6 ± 1037.2 ngh/ml) and nanosuspension (6770.4 ± 770.7 ngh/ml) but not suspension administration (966.0 ± 58.1 ngh/ml). However, distribution of DK-I-56–1 after solution was heavily influenced by its composition, and brain availability of nanosuspension was superior to that of solution formulation. In spontaneous locomotor activity test, the expected hyperlocomotor effect was observed after nanosuspension administration, without compromising impact of the vehicle/excipients used. Therefore, nanonization of drug compound assembled with proper selection of stabilizers may seemingly contribute further thorough testing of DK-I-56–1 preclinical efficacy.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Science",
title = "Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance",
volume = "152",
pages = "105432",
doi = "10.1016/j.ejps.2020.105432"
}

Mitrović, J., Divović, B., Knutson, D., Đoković, J., Vulić, P., Randjelović, D., Dobričić, V., Čalija, B., Cook, J., Savić, M. M.,& Savić, S.. (2020). Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance. in European Journal of Pharmaceutical Science
Elsevier., 152, 105432.
https://doi.org/10.1016/j.ejps.2020.105432

Mitrović J, Divović B, Knutson D, Đoković J, Vulić P, Randjelović D, Dobričić V, Čalija B, Cook J, Savić MM, Savić S. Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance. in European Journal of Pharmaceutical Science. 2020;152:105432.
doi:10.1016/j.ejps.2020.105432 .

Mitrović, Jelena, Divović, Branka, Knutson, Daniel, Đoković, Jelena, Vulić, Predrag, Randjelović, Danijela, Dobričić, Vladimir, Čalija, Bojan, Cook, James, Savić, Miroslav M., Savić, Snežana, "Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance" in European Journal of Pharmaceutical Science, 152 (2020):105432,
https://doi.org/10.1016/j.ejps.2020.105432 . .

TY  - JOUR
AU  - Mitrović, Jelena
AU  - Divović, Branka
AU  - Knutson, Daniel
AU  - Đoković, Jelena
AU  - Vulić, Predrag
AU  - Randjelović, Danijela
AU  - Dobričić, Vladimir
AU  - Čalija, Bojan
AU  - Cook, James
AU  - Savić, Miroslav M.
AU  - Savić, Snežana
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3635
AB  - DK-I-56–1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one), a recently developed deuterated pyrazoloquinolinone, has been recognized as a lead candidate for treatment of various neuropsychiatric disorders. During preclinical investigation of poorly water-soluble compounds such as DK-I-56–1, the application of nanotechnology could be advantageous due to improved safety and possibly increased bioavailability of nanosized formulation. DK-I-56–1 nanosuspensions stabilized by polysorbate 80, alone or in combination with poloxamers 188 i.e. 407 or D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared using a small-scale media milling device. With particle size 208.7–250.6 nm and polydispersity index <0.250, selected nanodiseprsions were stable for three weeks. Pharmacokinetic and biodistribution studies following intraperitoneal administration of three types of formulation in mice indicated high plasma DK-I-56–1 levels after solution (10,228.6 ± 1037.2 ngh/ml) and nanosuspension (6770.4 ± 770.7 ngh/ml) but not suspension administration (966.0 ± 58.1 ngh/ml). However, distribution of DK-I-56–1 after solution was heavily influenced by its composition, and brain availability of nanosuspension was superior to that of solution formulation. In spontaneous locomotor activity test, the expected hyperlocomotor effect was observed after nanosuspension administration, without compromising impact of the vehicle/excipients used. Therefore, nanonization of drug compound assembled with proper selection of stabilizers may seemingly contribute further thorough testing of DK-I-56–1 preclinical efficacy.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Science
T1  - Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance
VL  - 152
SP  - 105432
DO  - 10.1016/j.ejps.2020.105432
ER  - 

@article{
author = "Mitrović, Jelena and Divović, Branka and Knutson, Daniel and Đoković, Jelena and Vulić, Predrag and Randjelović, Danijela and Dobričić, Vladimir and Čalija, Bojan and Cook, James and Savić, Miroslav M. and Savić, Snežana",
year = "2020",
abstract = "DK-I-56–1 (7‑methoxy‑2-(4‑methoxy‑d3-phenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one), a recently developed deuterated pyrazoloquinolinone, has been recognized as a lead candidate for treatment of various neuropsychiatric disorders. During preclinical investigation of poorly water-soluble compounds such as DK-I-56–1, the application of nanotechnology could be advantageous due to improved safety and possibly increased bioavailability of nanosized formulation. DK-I-56–1 nanosuspensions stabilized by polysorbate 80, alone or in combination with poloxamers 188 i.e. 407 or D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared using a small-scale media milling device. With particle size 208.7–250.6 nm and polydispersity index <0.250, selected nanodiseprsions were stable for three weeks. Pharmacokinetic and biodistribution studies following intraperitoneal administration of three types of formulation in mice indicated high plasma DK-I-56–1 levels after solution (10,228.6 ± 1037.2 ngh/ml) and nanosuspension (6770.4 ± 770.7 ngh/ml) but not suspension administration (966.0 ± 58.1 ngh/ml). However, distribution of DK-I-56–1 after solution was heavily influenced by its composition, and brain availability of nanosuspension was superior to that of solution formulation. In spontaneous locomotor activity test, the expected hyperlocomotor effect was observed after nanosuspension administration, without compromising impact of the vehicle/excipients used. Therefore, nanonization of drug compound assembled with proper selection of stabilizers may seemingly contribute further thorough testing of DK-I-56–1 preclinical efficacy.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Science",
title = "Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance",
volume = "152",
pages = "105432",
doi = "10.1016/j.ejps.2020.105432"
}

Mitrović, J., Divović, B., Knutson, D., Đoković, J., Vulić, P., Randjelović, D., Dobričić, V., Čalija, B., Cook, J., Savić, M. M.,& Savić, S.. (2020). Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance. in European Journal of Pharmaceutical Science
Elsevier., 152, 105432.
https://doi.org/10.1016/j.ejps.2020.105432

Mitrović J, Divović B, Knutson D, Đoković J, Vulić P, Randjelović D, Dobričić V, Čalija B, Cook J, Savić MM, Savić S. Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance. in European Journal of Pharmaceutical Science. 2020;152:105432.
doi:10.1016/j.ejps.2020.105432 .

Mitrović, Jelena, Divović, Branka, Knutson, Daniel, Đoković, Jelena, Vulić, Predrag, Randjelović, Danijela, Dobričić, Vladimir, Čalija, Bojan, Cook, James, Savić, Miroslav M., Savić, Snežana, "Nanocrystal dispersion of DK-I-56–1, a poorly soluble pyrazoloquinolinone positive modulator of α6 GABAA receptors: Formulation approach toward improved in vivo performance" in European Journal of Pharmaceutical Science, 152 (2020):105432,
https://doi.org/10.1016/j.ejps.2020.105432 . .

TY  - JOUR
AU  - Nikolić, Ines
AU  - Mitsou, Evgenia
AU  - Pantelić, Ivana
AU  - Randjelović, Danijela
AU  - Marković, Bojan D.
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Lunter, Dominique Jasmin
AU  - Žugić, Ana
AU  - Savić, Snežana D.
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3386
AB  - The objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers.  Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml.  Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions’ interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cells) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ± 0.2% for the MCT nanoemulsions, 13.9 ± 0.1% and 14.0 ± 0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?
VL  - 142
SP  - 105135
DO  - 10.1016/j.ejps.2019.105135
ER  - 

@article{
author = "Nikolić, Ines and Mitsou, Evgenia and Pantelić, Ivana and Randjelović, Danijela and Marković, Bojan D. and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Lunter, Dominique Jasmin and Žugić, Ana and Savić, Snežana D.",
year = "2020",
abstract = "The objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers.  Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml.  Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions’ interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cells) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ± 0.2% for the MCT nanoemulsions, 13.9 ± 0.1% and 14.0 ± 0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?",
volume = "142",
pages = "105135",
doi = "10.1016/j.ejps.2019.105135"
}

Nikolić, I., Mitsou, E., Pantelić, I., Randjelović, D., Marković, B. D., Papadimitriou, V., Xenakis, A., Lunter, D. J., Žugić, A.,& Savić, S. D.. (2020). Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?. in European Journal of Pharmaceutical Sciences
Elsevier., 142, 105135.
https://doi.org/10.1016/j.ejps.2019.105135

Nikolić I, Mitsou E, Pantelić I, Randjelović D, Marković BD, Papadimitriou V, Xenakis A, Lunter DJ, Žugić A, Savić SD. Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?. in European Journal of Pharmaceutical Sciences. 2020;142:105135.
doi:10.1016/j.ejps.2019.105135 .

Nikolić, Ines, Mitsou, Evgenia, Pantelić, Ivana, Randjelović, Danijela, Marković, Bojan D., Papadimitriou, Vassiliki, Xenakis, Aristotelis, Lunter, Dominique Jasmin, Žugić, Ana, Savić, Snežana D., "Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?" in European Journal of Pharmaceutical Sciences, 142 (2020):105135,
https://doi.org/10.1016/j.ejps.2019.105135 . .

TY  - JOUR
AU  - Nikolić, Ines
AU  - Mitsou, Evgenia
AU  - Pantelić, Ivana
AU  - Randjelović, Danijela
AU  - Marković, Bojan D.
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Lunter, Dominique Jasmin
AU  - Žugić, Ana
AU  - Savić, Snežana D.
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3309
AB  - he objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers.  Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml.  Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions’ interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cells) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ± 0.2% for the MCT nanoemulsions, 13.9 ± 0.1% and 14.0 ± 0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?
VL  - 142
SP  - 105135
DO  - 10.1016/j.ejps.2019.105135
ER  - 

@article{
author = "Nikolić, Ines and Mitsou, Evgenia and Pantelić, Ivana and Randjelović, Danijela and Marković, Bojan D. and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Lunter, Dominique Jasmin and Žugić, Ana and Savić, Snežana D.",
year = "2020",
abstract = "he objective of this work was to develop low-energy nanoemulsions for enhanced dermal delivery of curcumin, using monoterpene compounds eucalyptol (EUC) and pinene (PIN) as chemical penetration enhancers.  Spontaneous emulsification was the preparation method. All formulations contained 10% of the oil phase (medium-chain triglycerides (MCT), or their mixture with EUC or PIN). Formulations were stabilized by the combination of polysorbate 80 and soybean lecithin (surfactant-to-oil-ratio=1). Concentration of curcumin was set to 3 mg/ml.  Average droplet diameter of all tested formulations ranged from 102 nm to 132 nm, but the ones containing monoterpenes had significantly smaller size compared to the MCT formulation. Such finding was profoundly studied through electron paramagnetic resonance spectroscopy, which proved that the presence of monoterpenes modified the nanoemulsions’ interfacial environment, resulting in droplet size reduction. The release study of curcumin (using Franz cells) demonstrated that the cumulative amount released after 6 h of the experiment was 10.1 ± 0.2% for the MCT nanoemulsions, 13.9 ± 0.1% and 14.0 ± 0.2% for PIN and EUC formulations, respectively. In vivo tape stripping revealed their performances in delivering curcumin into the skin, indicating the following order: EUC>MCT>PIN. The formulation with EUC was clearly the most successful, giving the highest cumulative amount of curcumin that penetrated per surface unit: 34.24±5.68 µg/cm2. The MCT formulation followed (30.62±2.61 µg/cm2) and, finally, the one with PIN (21.61±0.11 µg/cm2). These results corelated with curcumin's solubility in the chosen oils: 4.18±0.02 mg/ml for EUC, 1.67±0.04 mg/ml for MCT and 0.21±0.01 mg/ml for PIN. Probably, higher solubility in the oil phase of the nanoemulsion promoted curcumin's solubility in the superficial skin layers, providing enhanced penetration.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?",
volume = "142",
pages = "105135",
doi = "10.1016/j.ejps.2019.105135"
}

Nikolić, I., Mitsou, E., Pantelić, I., Randjelović, D., Marković, B. D., Papadimitriou, V., Xenakis, A., Lunter, D. J., Žugić, A.,& Savić, S. D.. (2020). Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?. in European Journal of Pharmaceutical Sciences
Elsevier., 142, 105135.
https://doi.org/10.1016/j.ejps.2019.105135

Nikolić I, Mitsou E, Pantelić I, Randjelović D, Marković BD, Papadimitriou V, Xenakis A, Lunter DJ, Žugić A, Savić SD. Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?. in European Journal of Pharmaceutical Sciences. 2020;142:105135.
doi:10.1016/j.ejps.2019.105135 .

Nikolić, Ines, Mitsou, Evgenia, Pantelić, Ivana, Randjelović, Danijela, Marković, Bojan D., Papadimitriou, Vassiliki, Xenakis, Aristotelis, Lunter, Dominique Jasmin, Žugić, Ana, Savić, Snežana D., "Microstructure and biopharmaceutical performances of curcumin-loaded low-energy nanoemulsions containing eucalyptol and pinene: Terpenes’ role overcome penetration enhancement effect?" in European Journal of Pharmaceutical Sciences, 142 (2020):105135,
https://doi.org/10.1016/j.ejps.2019.105135 . .

TY  - JOUR
AU  - Pantelić, Ivana
AU  - Lukić, Milica
AU  - Gojgić-Cvijović, Gordana
AU  - Jakovljević, Dragica
AU  - Nikolić, Ines
AU  - Jasmin Lunterc, Dominique
AU  - Daniels, Rolf
AU  - Savić, Snežana D.
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3349
AB  - Ongoing demand in sustainable and biocompatible drug dosage forms is reflected in the search for novel pharmaceutical excipients with equal properties. A group of microbial exopolysaccharides offers a variety of biopolymers with many alleged uses and effects. This study aims to assess applicative properties of levan obtained from Bacillus licheniformis NS032, focusing on its potential co-stabilizing and drug release-controlling functions in pertaining emulsion systems. Despite its high molecular weight and partial existence in globular nanometric structures (180-190 nm), levan was successfully incorporated into both tested colloidal systems: those stabilized with synthetic/anionic or natural-origin/non-ionic emulsifiers. In the tested levan concentrations range (0.2-3.0% w/w) the monitored flow and thermal parameters failed to show linear concentration dependence, which prompted us to revisit certain colloidal fundamentals of this biopolymer. Being a part of the external phase of the investigated emulsion systems, levan contributed to formation of a matrix-like environment, offering additional stabilization of the microstructure and rheology modifying properties (hysteresis loop elevation as high as 4167±98 to 20792±3166 Pa•s−1), especially in case of the samples where lamellar liquid crystalline formation occurred. Apart from its good water solubility and considerable conformational flexibility, the investigated homofructan easily saturated the external phase of the samples stabilized with a conventional anionic emulsifier, leading to similar properties of 0.2% and 3.0% levan-containing samples. After closer consideration of thermal and release behavior, this was considered as a favorable property for a novel excipient, offering tailored formulation characteristics even with lower levan concentrations, consequently not compromising the potential cost of the final drug dosage form.
PB  - Elsevier
T2  - European Journal of Pharmaceutical Sciences
T1  - Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application
VL  - 142
SP  - 105109
DO  - 10.1016/j.ejps.2019.105109
ER  - 

@article{
author = "Pantelić, Ivana and Lukić, Milica and Gojgić-Cvijović, Gordana and Jakovljević, Dragica and Nikolić, Ines and Jasmin Lunterc, Dominique and Daniels, Rolf and Savić, Snežana D.",
year = "2020",
abstract = "Ongoing demand in sustainable and biocompatible drug dosage forms is reflected in the search for novel pharmaceutical excipients with equal properties. A group of microbial exopolysaccharides offers a variety of biopolymers with many alleged uses and effects. This study aims to assess applicative properties of levan obtained from Bacillus licheniformis NS032, focusing on its potential co-stabilizing and drug release-controlling functions in pertaining emulsion systems. Despite its high molecular weight and partial existence in globular nanometric structures (180-190 nm), levan was successfully incorporated into both tested colloidal systems: those stabilized with synthetic/anionic or natural-origin/non-ionic emulsifiers. In the tested levan concentrations range (0.2-3.0% w/w) the monitored flow and thermal parameters failed to show linear concentration dependence, which prompted us to revisit certain colloidal fundamentals of this biopolymer. Being a part of the external phase of the investigated emulsion systems, levan contributed to formation of a matrix-like environment, offering additional stabilization of the microstructure and rheology modifying properties (hysteresis loop elevation as high as 4167±98 to 20792±3166 Pa•s−1), especially in case of the samples where lamellar liquid crystalline formation occurred. Apart from its good water solubility and considerable conformational flexibility, the investigated homofructan easily saturated the external phase of the samples stabilized with a conventional anionic emulsifier, leading to similar properties of 0.2% and 3.0% levan-containing samples. After closer consideration of thermal and release behavior, this was considered as a favorable property for a novel excipient, offering tailored formulation characteristics even with lower levan concentrations, consequently not compromising the potential cost of the final drug dosage form.",
publisher = "Elsevier",
journal = "European Journal of Pharmaceutical Sciences",
title = "Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application",
volume = "142",
pages = "105109",
doi = "10.1016/j.ejps.2019.105109"
}

Pantelić, I., Lukić, M., Gojgić-Cvijović, G., Jakovljević, D., Nikolić, I., Jasmin Lunterc, D., Daniels, R.,& Savić, S. D.. (2020). Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application. in European Journal of Pharmaceutical Sciences
Elsevier., 142, 105109.
https://doi.org/10.1016/j.ejps.2019.105109

Pantelić I, Lukić M, Gojgić-Cvijović G, Jakovljević D, Nikolić I, Jasmin Lunterc D, Daniels R, Savić SD. Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application. in European Journal of Pharmaceutical Sciences. 2020;142:105109.
doi:10.1016/j.ejps.2019.105109 .

Pantelić, Ivana, Lukić, Milica, Gojgić-Cvijović, Gordana, Jakovljević, Dragica, Nikolić, Ines, Jasmin Lunterc, Dominique, Daniels, Rolf, Savić, Snežana D., "Bacillus licheniformis levan as a functional biopolymer in topical drug dosage forms: From basic colloidal considerations to actual pharmaceutical application" in European Journal of Pharmaceutical Sciences, 142 (2020):105109,
https://doi.org/10.1016/j.ejps.2019.105109 . .

TY  - JOUR
AU  - Pajic, Natasa Bubic
AU  - Nikolić, Ines
AU  - Mitsou, Evgenia
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Randjelović, Danijela
AU  - Dobricic, Vladimir
AU  - Smitran, Aleksandra
AU  - Cekic, Nebojsa
AU  - Calija, Bojan
AU  - Savić, Snežana D.
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4291
AB  - The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.
PB  - Elsevier
T2  - Journal of Molecular Liquids
T1  - Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties
VL  - 272
SP  - 746
EP  - 758
DO  - 10.1016/j.molliq.2018.10.002
ER  - 

@article{
author = "Pajic, Natasa Bubic and Nikolić, Ines and Mitsou, Evgenia and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Randjelović, Danijela and Dobricic, Vladimir and Smitran, Aleksandra and Cekic, Nebojsa and Calija, Bojan and Savić, Snežana D.",
year = "2018",
abstract = "The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.",
publisher = "Elsevier",
journal = "Journal of Molecular Liquids",
title = "Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties",
volume = "272",
pages = "746-758",
doi = "10.1016/j.molliq.2018.10.002"
}

Pajic, N. B., Nikolić, I., Mitsou, E., Papadimitriou, V., Xenakis, A., Randjelović, D., Dobricic, V., Smitran, A., Cekic, N., Calija, B.,& Savić, S. D.. (2018). Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. in Journal of Molecular Liquids
Elsevier., 272, 746-758.
https://doi.org/10.1016/j.molliq.2018.10.002

Pajic NB, Nikolić I, Mitsou E, Papadimitriou V, Xenakis A, Randjelović D, Dobricic V, Smitran A, Cekic N, Calija B, Savić SD. Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. in Journal of Molecular Liquids. 2018;272:746-758.
doi:10.1016/j.molliq.2018.10.002 .

Pajic, Natasa Bubic, Nikolić, Ines, Mitsou, Evgenia, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Randjelović, Danijela, Dobricic, Vladimir, Smitran, Aleksandra, Cekic, Nebojsa, Calija, Bojan, Savić, Snežana D., "Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties" in Journal of Molecular Liquids, 272 (2018):746-758,
https://doi.org/10.1016/j.molliq.2018.10.002 . .

TY  - JOUR
AU  - Nikolić, Ines
AU  - Lunter, Dominique Jasmin
AU  - Randjelović, Danijela
AU  - Žugić, Ana
AU  - Tadić, Vanja
AU  - Marković, Bojan D.
AU  - Cekic, Nebojsa
AU  - Živković, Lada
AU  - Topalovic, Dijana
AU  - Spremo-Potparević, Biljana
AU  - Daniels, Rolf
AU  - Savić, Snežana D.
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3719
AB  - The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI  LT  0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application
VL  - 550
IS  - 1-2
SP  - 333
EP  - 346
DO  - 10.1016/j.ijpharm.2018.08.060
ER  - 

@article{
author = "Nikolić, Ines and Lunter, Dominique Jasmin and Randjelović, Danijela and Žugić, Ana and Tadić, Vanja and Marković, Bojan D. and Cekic, Nebojsa and Živković, Lada and Topalovic, Dijana and Spremo-Potparević, Biljana and Daniels, Rolf and Savić, Snežana D.",
year = "2018",
abstract = "The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI  LT  0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application",
volume = "550",
number = "1-2",
pages = "333-346",
doi = "10.1016/j.ijpharm.2018.08.060"
}

Nikolić, I., Lunter, D. J., Randjelović, D., Žugić, A., Tadić, V., Marković, B. D., Cekic, N., Živković, L., Topalovic, D., Spremo-Potparević, B., Daniels, R.,& Savić, S. D.. (2018). Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application. in International Journal of Pharmaceutics
Elsevier., 550(1-2), 333-346.
https://doi.org/10.1016/j.ijpharm.2018.08.060

Nikolić I, Lunter DJ, Randjelović D, Žugić A, Tadić V, Marković BD, Cekic N, Živković L, Topalovic D, Spremo-Potparević B, Daniels R, Savić SD. Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application. in International Journal of Pharmaceutics. 2018;550(1-2):333-346.
doi:10.1016/j.ijpharm.2018.08.060 .

Nikolić, Ines, Lunter, Dominique Jasmin, Randjelović, Danijela, Žugić, Ana, Tadić, Vanja, Marković, Bojan D., Cekic, Nebojsa, Živković, Lada, Topalovic, Dijana, Spremo-Potparević, Biljana, Daniels, Rolf, Savić, Snežana D., "Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application" in International Journal of Pharmaceutics, 550, no. 1-2 (2018):333-346,
https://doi.org/10.1016/j.ijpharm.2018.08.060 . .

TY  - JOUR
AU  - Pajic, Natasa Bubic
AU  - Nikolić, Ines
AU  - Mitsou, Evgenia
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Randjelović, Danijela
AU  - Dobricic, Vladimir
AU  - Smitran, Aleksandra
AU  - Cekic, Nebojsa
AU  - Calija, Bojan
AU  - Savić, Snežana D.
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2360
AB  - The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.
PB  - Elsevier
T2  - Journal of Molecular Liquids
T1  - Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties
VL  - 272
SP  - 746
EP  - 758
DO  - 10.1016/j.molliq.2018.10.002
ER  - 

@article{
author = "Pajic, Natasa Bubic and Nikolić, Ines and Mitsou, Evgenia and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Randjelović, Danijela and Dobricic, Vladimir and Smitran, Aleksandra and Cekic, Nebojsa and Calija, Bojan and Savić, Snežana D.",
year = "2018",
abstract = "The aim of this study was development of biocompatible topical microemulsions (MEs) for incorporation and improved dermal delivery of sertaconazole nitrate (SN). For this purpose, phase behavior and microstructure of pseudo-ternary glycereth-7-caprylate/caprate (Emanon EV-E, EV)/cosurfactant/Capryol (TM) 90/water systems were investigated. Furhermore, the influence of these properties on the drug skin delivery was also assessed. Expansion of ME single-phase regions with the use of short chain alcohols was a consequence of the more fluid interface when compared to other investigated systems, which was confirmed by electron paramagnetic resonance spectroscopy-EPR. The chosen bicontinuous to inverted bicontinuous formulations were assessed against the ME based on polysorbate 80 as referent sample. Despite incorporation of SN within the selected formulations induced similar alternations in electrical conductivity, viscosity and pH values, obtained EPR spectra suggested different SN localization: within the oil phase (for most of the EV based formulations), or interacting with the interface (polysorbate 80 based formulation). Due to higher in vitro drug release (12.24%-18.53%), ex vivo SN penetration into porcine ear skin (dermal retention Enhancement Ratio (ERO) ranged from 2.66 to 4.25) and pronounced antifungal activity, the chosen MEs represent promising vehicles for dermal delivery of SN in treatment of cutaneous fungal infections. The biopharmaceutical and skin performance differences obtained with different formulations were possible to be explained on the basis of their physicochemical characteristics.",
publisher = "Elsevier",
journal = "Journal of Molecular Liquids",
title = "Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties",
volume = "272",
pages = "746-758",
doi = "10.1016/j.molliq.2018.10.002"
}

Pajic, N. B., Nikolić, I., Mitsou, E., Papadimitriou, V., Xenakis, A., Randjelović, D., Dobricic, V., Smitran, A., Cekic, N., Calija, B.,& Savić, S. D.. (2018). Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. in Journal of Molecular Liquids
Elsevier., 272, 746-758.
https://doi.org/10.1016/j.molliq.2018.10.002

Pajic NB, Nikolić I, Mitsou E, Papadimitriou V, Xenakis A, Randjelović D, Dobricic V, Smitran A, Cekic N, Calija B, Savić SD. Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties. in Journal of Molecular Liquids. 2018;272:746-758.
doi:10.1016/j.molliq.2018.10.002 .

Pajic, Natasa Bubic, Nikolić, Ines, Mitsou, Evgenia, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Randjelović, Danijela, Dobricic, Vladimir, Smitran, Aleksandra, Cekic, Nebojsa, Calija, Bojan, Savić, Snežana D., "Biocompatible microemulsions for improved dermal delivery of sertaconazole nitrate: Phase behavior study and microstructure influence on drug biopharamaceutical properties" in Journal of Molecular Liquids, 272 (2018):746-758,
https://doi.org/10.1016/j.molliq.2018.10.002 . .

TY  - JOUR
AU  - Nikolić, Ines
AU  - Lunter, Dominique Jasmin
AU  - Randjelović, Danijela
AU  - Žugić, Ana
AU  - Tadić, Vanja
AU  - Marković, Bojan D.
AU  - Cekic, Nebojsa
AU  - Živković, Lada
AU  - Topalovic, Dijana
AU  - Spremo-Potparević, Biljana
AU  - Daniels, Rolf
AU  - Savić, Snežana D.
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2425
AB  - The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI  LT  0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application
VL  - 550
IS  - 1-2
SP  - 333
EP  - 346
DO  - 10.1016/j.ijpharm.2018.08.060
ER  - 

@article{
author = "Nikolić, Ines and Lunter, Dominique Jasmin and Randjelović, Danijela and Žugić, Ana and Tadić, Vanja and Marković, Bojan D. and Cekic, Nebojsa and Živković, Lada and Topalovic, Dijana and Spremo-Potparević, Biljana and Daniels, Rolf and Savić, Snežana D.",
year = "2018",
abstract = "The objective of this work was to investigate and profoundly characterize low-energy nanoemulsions as multifunctional carriers, with slight reference to dermal administration. An evidence-based approach was offered for deepening the knowledge on their formation via spontaneous emulsification. Curcumin, a compound of natural origin, potentially powerful therapeutic, was chosen as a model API. Due to curcumin's demanding properties (instability, poor solubility, low permeability), its potentials remain unreached. Low-energy nanoemulsions were considered carriers capable of overcoming imposed obstacles. Formulation consisting of Polysorbate 80 and soybean lecithin as stabilizers (9:1, 10%), medium-chain triglycerides as the oil phase (10%) and ultrapure water was selected for curcumin incorporation in 3 different concentrations (1, 2 and 3 mg/mL). Physicochemical stability was demonstrated during 3 months of monitoring (mean droplet size: 111.3-146.8 nm; PDI  LT  0.2; pH: 4.73-5.73). Curcumin's release from developed vehicles followed Higuchi's kinetics. DPPH (IC50 = 0.1187 mg/ mL) and FRAP (1.19 +/- 0.02 mmol/g) assays confirmed that curcumin acts as a potent antioxidant through different mechanisms, with no alterations after incorporation in the formulation. High biocompatibility in line with antigenotoxic activity of curcumin-loaded formulations (protective and reparative) was estimated through Comet assay. A multidisciplinary approach is needed to fully characterize developed systems, directing them to more concrete application possibilities.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application",
volume = "550",
number = "1-2",
pages = "333-346",
doi = "10.1016/j.ijpharm.2018.08.060"
}

Nikolić, I., Lunter, D. J., Randjelović, D., Žugić, A., Tadić, V., Marković, B. D., Cekic, N., Živković, L., Topalovic, D., Spremo-Potparević, B., Daniels, R.,& Savić, S. D.. (2018). Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application. in International Journal of Pharmaceutics
Elsevier., 550(1-2), 333-346.
https://doi.org/10.1016/j.ijpharm.2018.08.060

Nikolić I, Lunter DJ, Randjelović D, Žugić A, Tadić V, Marković BD, Cekic N, Živković L, Topalovic D, Spremo-Potparević B, Daniels R, Savić SD. Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application. in International Journal of Pharmaceutics. 2018;550(1-2):333-346.
doi:10.1016/j.ijpharm.2018.08.060 .

Nikolić, Ines, Lunter, Dominique Jasmin, Randjelović, Danijela, Žugić, Ana, Tadić, Vanja, Marković, Bojan D., Cekic, Nebojsa, Živković, Lada, Topalovic, Dijana, Spremo-Potparević, Biljana, Daniels, Rolf, Savić, Snežana D., "Curcumin-loaded low-energy nanoemulsions as a prototype of multifunctional vehicles for different administration routes: Physicochemical and in vitro peculiarities important for dermal application" in International Journal of Pharmaceutics, 550, no. 1-2 (2018):333-346,
https://doi.org/10.1016/j.ijpharm.2018.08.060 . .

TY  - JOUR
AU  - Isailovic, Tanja
AU  - Dordevic, Sanela
AU  - Marković, Bojan D.
AU  - Randjelović, Danijela
AU  - Cekic, Nebojsa
AU  - Lukić, Milica
AU  - Pantelić, Ivana
AU  - Daniels, Rolf
AU  - Savić, Snežana D.
PY  - 2016
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1846
AB  - We aimed to develop lecithin-based nanoemulsions intended for effective aceclofenac (ACF) skin delivery utilizing sucrose esters [sucrose palmitate (SP) and sucrose stearate (SS)] as additional stabilizers and penetration enhancers. To find the suitable surfactant mixtures and levels of process variables (homogenization pressure and number of cycles-high pressure homogenization manufacturing method) that result in drug-loaded nanoemulsions with minimal droplet size and narrow size distribution, a combined mixture-process experimental design was employed. Based on optimization data, selected nanoemulsions were evaluated regarding morphology, surface charge, drug-excipient interactions, physical stability, and in vivo skin performances (skin penetration and irritation potential). The predicted physicochemical properties and storage stability were proved satisfying for ACF-loaded nanoemulsions containing 2% of SP in the blend with 0%-1% of SS and 1%-2% of egg lecithin (produced at 50 degrees C/20 cycles/800 bar). Additionally, the in vivo tape stripping demonstrated superior ACF skin absorption from these nanoemulsions, particularly from those containing 2% of SP, 0.5% of SS, and 1.5% of egg lecithin, when comparing with the sample costabilized by conventional surfactant-polysorbate 80. In summary, the combined mixture-process experimental design was shown as a feasible tool for formulation development of multisurfactant-based nanosized delivery systems with potentially improved overall product performances.
PB  - Wiley, Hoboken
T2  - Journal of Pharmaceutical Sciences
T1  - Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design
VL  - 105
IS  - 1
SP  - 308
EP  - 323
DO  - 10.1002/jps.24706
ER  - 

@article{
author = "Isailovic, Tanja and Dordevic, Sanela and Marković, Bojan D. and Randjelović, Danijela and Cekic, Nebojsa and Lukić, Milica and Pantelić, Ivana and Daniels, Rolf and Savić, Snežana D.",
year = "2016",
abstract = "We aimed to develop lecithin-based nanoemulsions intended for effective aceclofenac (ACF) skin delivery utilizing sucrose esters [sucrose palmitate (SP) and sucrose stearate (SS)] as additional stabilizers and penetration enhancers. To find the suitable surfactant mixtures and levels of process variables (homogenization pressure and number of cycles-high pressure homogenization manufacturing method) that result in drug-loaded nanoemulsions with minimal droplet size and narrow size distribution, a combined mixture-process experimental design was employed. Based on optimization data, selected nanoemulsions were evaluated regarding morphology, surface charge, drug-excipient interactions, physical stability, and in vivo skin performances (skin penetration and irritation potential). The predicted physicochemical properties and storage stability were proved satisfying for ACF-loaded nanoemulsions containing 2% of SP in the blend with 0%-1% of SS and 1%-2% of egg lecithin (produced at 50 degrees C/20 cycles/800 bar). Additionally, the in vivo tape stripping demonstrated superior ACF skin absorption from these nanoemulsions, particularly from those containing 2% of SP, 0.5% of SS, and 1.5% of egg lecithin, when comparing with the sample costabilized by conventional surfactant-polysorbate 80. In summary, the combined mixture-process experimental design was shown as a feasible tool for formulation development of multisurfactant-based nanosized delivery systems with potentially improved overall product performances.",
publisher = "Wiley, Hoboken",
journal = "Journal of Pharmaceutical Sciences",
title = "Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design",
volume = "105",
number = "1",
pages = "308-323",
doi = "10.1002/jps.24706"
}

Isailovic, T., Dordevic, S., Marković, B. D., Randjelović, D., Cekic, N., Lukić, M., Pantelić, I., Daniels, R.,& Savić, S. D.. (2016). Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design. in Journal of Pharmaceutical Sciences
Wiley, Hoboken., 105(1), 308-323.
https://doi.org/10.1002/jps.24706

Isailovic T, Dordevic S, Marković BD, Randjelović D, Cekic N, Lukić M, Pantelić I, Daniels R, Savić SD. Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design. in Journal of Pharmaceutical Sciences. 2016;105(1):308-323.
doi:10.1002/jps.24706 .

Isailovic, Tanja, Dordevic, Sanela, Marković, Bojan D., Randjelović, Danijela, Cekic, Nebojsa, Lukić, Milica, Pantelić, Ivana, Daniels, Rolf, Savić, Snežana D., "Biocompatible Nanoemulsions for Improved Aceclofenac Skin Delivery: Formulation Approach Using Combined Mixture-Process Experimental Design" in Journal of Pharmaceutical Sciences, 105, no. 1 (2016):308-323,
https://doi.org/10.1002/jps.24706 . .

TY  - JOUR
AU  - Dordevic, Sanela M
AU  - Cekic, Nebojsa
AU  - Savić, Miroslav M.
AU  - Isailovic, Tanja M
AU  - Randjelović, Danijela
AU  - Marković, Bojan D.
AU  - Savić, Saša R.
AU  - Stamenic, Tamara Timic
AU  - Daniels, Rolf
AU  - Savić, Snežana D.
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1697
AB  - This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution  LT 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation
VL  - 493
IS  - 1-2
SP  - 40
EP  - 54
DO  - 10.1016/j.ijpharm.2015.07.007
ER  - 

@article{
author = "Dordevic, Sanela M and Cekic, Nebojsa and Savić, Miroslav M. and Isailovic, Tanja M and Randjelović, Danijela and Marković, Bojan D. and Savić, Saša R. and Stamenic, Tamara Timic and Daniels, Rolf and Savić, Snežana D.",
year = "2015",
abstract = "This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution  LT 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation",
volume = "493",
number = "1-2",
pages = "40-54",
doi = "10.1016/j.ijpharm.2015.07.007"
}

Dordevic, S. M., Cekic, N., Savić, M. M., Isailovic, T. M., Randjelović, D., Marković, B. D., Savić, S. R., Stamenic, T. T., Daniels, R.,& Savić, S. D.. (2015). Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation. in International Journal of Pharmaceutics
Elsevier., 493(1-2), 40-54.
https://doi.org/10.1016/j.ijpharm.2015.07.007

Dordevic SM, Cekic N, Savić MM, Isailovic TM, Randjelović D, Marković BD, Savić SR, Stamenic TT, Daniels R, Savić SD. Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation. in International Journal of Pharmaceutics. 2015;493(1-2):40-54.
doi:10.1016/j.ijpharm.2015.07.007 .

Dordevic, Sanela M, Cekic, Nebojsa, Savić, Miroslav M., Isailovic, Tanja M, Randjelović, Danijela, Marković, Bojan D., Savić, Saša R., Stamenic, Tamara Timic, Daniels, Rolf, Savić, Snežana D., "Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation" in International Journal of Pharmaceutics, 493, no. 1-2 (2015):40-54,
https://doi.org/10.1016/j.ijpharm.2015.07.007 . .

TY  - JOUR
AU  - Todosijević, Marija
AU  - Savić, Miroslav M.
AU  - Batinić, Bojan B.
AU  - Marković, Bojan D.
AU  - Gasperlin, Mirjana
AU  - Randjelović, Danijela
AU  - Lukić, Milica
AU  - Savić, Snežana D.
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1805
AB  - To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester-over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81 +/- 5.97 and 60.86 +/- 3.67 vs. 27.00 +/- 5.09 mu g/cm(2), and its maximum plasma concentrations 275.57 +/- 109.49 and 281.31 +/- 76.76 vs. 150.23 +/- 69.74 ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance
VL  - 496
IS  - 2
SP  - 931
EP  - 941
DO  - 10.1016/j.ijpharm.2015.10.048
ER  - 

@article{
author = "Todosijević, Marija and Savić, Miroslav M. and Batinić, Bojan B. and Marković, Bojan D. and Gasperlin, Mirjana and Randjelović, Danijela and Lukić, Milica and Savić, Snežana D.",
year = "2015",
abstract = "To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester-over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81 +/- 5.97 and 60.86 +/- 3.67 vs. 27.00 +/- 5.09 mu g/cm(2), and its maximum plasma concentrations 275.57 +/- 109.49 and 281.31 +/- 76.76 vs. 150.23 +/- 69.74 ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance",
volume = "496",
number = "2",
pages = "931-941",
doi = "10.1016/j.ijpharm.2015.10.048"
}

Todosijević, M., Savić, M. M., Batinić, B. B., Marković, B. D., Gasperlin, M., Randjelović, D., Lukić, M.,& Savić, S. D.. (2015). Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance. in International Journal of Pharmaceutics
Elsevier., 496(2), 931-941.
https://doi.org/10.1016/j.ijpharm.2015.10.048

Todosijević M, Savić MM, Batinić BB, Marković BD, Gasperlin M, Randjelović D, Lukić M, Savić SD. Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance. in International Journal of Pharmaceutics. 2015;496(2):931-941.
doi:10.1016/j.ijpharm.2015.10.048 .

Todosijević, Marija, Savić, Miroslav M., Batinić, Bojan B., Marković, Bojan D., Gasperlin, Mirjana, Randjelović, Danijela, Lukić, Milica, Savić, Snežana D., "Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance" in International Journal of Pharmaceutics, 496, no. 2 (2015):931-941,
https://doi.org/10.1016/j.ijpharm.2015.10.048 . .

TY  - JOUR
AU  - Dordevic, Sanela M
AU  - Cekic, Nebojsa
AU  - Savić, Miroslav M.
AU  - Isailovic, Tanja M
AU  - Randjelović, Danijela
AU  - Marković, Bojan D.
AU  - Savić, Saša R.
AU  - Stamenic, Tamara Timic
AU  - Daniels, Rolf
AU  - Savić, Snežana D.
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3201
AB  - This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution  LT 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation
VL  - 493
IS  - 1-2
SP  - 40
EP  - 54
DO  - 10.1016/j.ijpharm.2015.07.007
ER  - 

@article{
author = "Dordevic, Sanela M and Cekic, Nebojsa and Savić, Miroslav M. and Isailovic, Tanja M and Randjelović, Danijela and Marković, Bojan D. and Savić, Saša R. and Stamenic, Tamara Timic and Daniels, Rolf and Savić, Snežana D.",
year = "2015",
abstract = "This paper describes design and evaluation of parenteral lecithin-based nanoemulsions intended for brain delivery of risperidone, a poorly water-soluble psychopharmacological drug. The nanoemulsions were prepared through cold/hot high pressure homogenization and characterized regarding droplet size, polydispersity, surface charge, morphology, drug-vehicle interactions, and physical stability. To estimate the simultaneous influence of nanoemulsion formulation and preparation parameters-co-emulsifier type, aqueous phase type, homogenization temperature-on the critical quality attributes of developed nanoemulsions, a general factorial experimental design was applied. From the established design space and stability data, promising risperidone-loaded nanoemulsions (mean size about 160 nm, size distribution  LT 0.15, zeta potential around -50 mV), containing sodium oleate in the aqueous phase and polysorbate 80, poloxamer 188 or Solutol (R) HS15 as co-emulsifier, were produced by hot homogenization and their ability to improve risperidone delivery to the brain was assessed in rats. Pharmacokinetic study demonstrated erratic brain profiles of risperidone following intraperitoneal administration in selected nanoemulsions, most probably due to their different droplet surface properties (different composition of the stabilizing layer). Namely, polysorbate 80-costabilized nanoemulsion showed increased (1.4-7.4-fold higher) risperidone brain availability compared to other nanoemulsions and drug solution, suggesting this nanoemulsion as a promising carrier worth exploring further for brain targeting.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation",
volume = "493",
number = "1-2",
pages = "40-54",
doi = "10.1016/j.ijpharm.2015.07.007"
}

Dordevic, S. M., Cekic, N., Savić, M. M., Isailovic, T. M., Randjelović, D., Marković, B. D., Savić, S. R., Stamenic, T. T., Daniels, R.,& Savić, S. D.. (2015). Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation. in International Journal of Pharmaceutics
Elsevier., 493(1-2), 40-54.
https://doi.org/10.1016/j.ijpharm.2015.07.007

Dordevic SM, Cekic N, Savić MM, Isailovic TM, Randjelović D, Marković BD, Savić SR, Stamenic TT, Daniels R, Savić SD. Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation. in International Journal of Pharmaceutics. 2015;493(1-2):40-54.
doi:10.1016/j.ijpharm.2015.07.007 .

Dordevic, Sanela M, Cekic, Nebojsa, Savić, Miroslav M., Isailovic, Tanja M, Randjelović, Danijela, Marković, Bojan D., Savić, Saša R., Stamenic, Tamara Timic, Daniels, Rolf, Savić, Snežana D., "Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation" in International Journal of Pharmaceutics, 493, no. 1-2 (2015):40-54,
https://doi.org/10.1016/j.ijpharm.2015.07.007 . .

TY  - JOUR
AU  - Todosijević, Marija
AU  - Savić, Miroslav M.
AU  - Batinić, Bojan B.
AU  - Marković, Bojan D.
AU  - Gasperlin, Mirjana
AU  - Randjelović, Danijela
AU  - Lukić, Milica
AU  - Savić, Snežana D.
PY  - 2015
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3202
AB  - To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester-over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81 +/- 5.97 and 60.86 +/- 3.67 vs. 27.00 +/- 5.09 mu g/cm(2), and its maximum plasma concentrations 275.57 +/- 109.49 and 281.31 +/- 76.76 vs. 150.23 +/- 69.74 ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance
VL  - 496
IS  - 2
SP  - 931
EP  - 941
DO  - 10.1016/j.ijpharm.2015.10.048
ER  - 

@article{
author = "Todosijević, Marija and Savić, Miroslav M. and Batinić, Bojan B. and Marković, Bojan D. and Gasperlin, Mirjana and Randjelović, Danijela and Lukić, Milica and Savić, Snežana D.",
year = "2015",
abstract = "To elaborate the decisive role of surfactants in promotion of aceclofenac' skin absorption, potentially avoiding irritation, we developed non-ionic microemulsions varying natural or synthetic surfactants: sucrose esters (laurate or myristate) vs. polysorbate 80. A comprehensive physicochemical characterization indicated no significant influence of the solubilized nonsteroidal anti-inflammatory drug on the bicontinuous structure of blank formulations. To evaluate skin tolerability of isopropyl alcohol, a sucrose ester-based microemulsion containing transcutol P as a cosurfactant was also developed. The measured skin parameters strongly depended on the (co)surfactant type, showing higher compatibility of the microemulsions containing sucrose ester and isopropyl alcohol. In vitro release results, in vivo tape stripping and pharmacokinetics in rats confirmed superiority of the sucrose ester-over polysorbate-based microemulsions (total amounts of aceclofenac penetrated 60.81 +/- 5.97 and 60.86 +/- 3.67 vs. 27.00 +/- 5.09 mu g/cm(2), and its maximum plasma concentrations 275.57 +/- 109.49 and 281.31 +/- 76.76 vs. 150.23 +/- 69.74 ng/ml for sucrose laurate- and myristate- vs. polysorbate 80-based microemulsions, respectively). Hence, sugar-based excipients increased delivery of aceclofenac through stratum corneum by increasing its fluidity, showing overall more satisfying safety profiles. In conclusion, sucrose ester-based microemulsions proved to be promising carriers for dermal/transdermal aceclofenac delivery.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance",
volume = "496",
number = "2",
pages = "931-941",
doi = "10.1016/j.ijpharm.2015.10.048"
}

Todosijević, M., Savić, M. M., Batinić, B. B., Marković, B. D., Gasperlin, M., Randjelović, D., Lukić, M.,& Savić, S. D.. (2015). Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance. in International Journal of Pharmaceutics
Elsevier., 496(2), 931-941.
https://doi.org/10.1016/j.ijpharm.2015.10.048

Todosijević M, Savić MM, Batinić BB, Marković BD, Gasperlin M, Randjelović D, Lukić M, Savić SD. Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance. in International Journal of Pharmaceutics. 2015;496(2):931-941.
doi:10.1016/j.ijpharm.2015.10.048 .

Todosijević, Marija, Savić, Miroslav M., Batinić, Bojan B., Marković, Bojan D., Gasperlin, Mirjana, Randjelović, Danijela, Lukić, Milica, Savić, Snežana D., "Biocompatible microemulsions of a model NSAID for skin delivery: A decisive role of surfactants in skin penetration/irritation profiles and pharmacokinetic performance" in International Journal of Pharmaceutics, 496, no. 2 (2015):931-941,
https://doi.org/10.1016/j.ijpharm.2015.10.048 . .