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  - 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  - 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  - 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 . .