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  - 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  - 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 . .