TY  - JOUR
AU  - Đoković, Jelena
AU  - Demisli, Sortiria
AU  - Savić, Sanela M.
AU  - Savić, Saša R.
AU  - Randjelović, Danijela V.
AU  - Marković, Bojan
AU  - Pantelić, Ivana
AU  - Mitrović, Jelena
AU  - Stanković, Tijana
AU  - Papadimitrou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Savić, Snežana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5651
AB  - Nanoemulsions (NEs) are frequently used in the food, cosmetics and pharmaceutical industries to deliver nutraceuticals, pharmaceutical or cosmetic active ingredients. When administering NEs parenterally, various stabilisers are added to prevent rapid plasma clearance and to successfully deliver the active ingredient to the target site. For this purpose, PEGylation is often used to prolong the circulation time of the droplets. However, the problem is to determine the optimal concentration of the PEGylating agent – the PEGylation efficacy – that ensures adequate surface protection. This is a particular challenge when the active ingredient is incorporated into the stabilising layer, where any changes could disrupt the stability of the droplet. For this reason, we aimed to determine the optimal concentration of PEG2000-DSPE for surface protection of curcumin-loaded NEs for parenteral administration using electron paramagnetic resonance (EPR) spectroscopy. NEs were prepared using the high pressure homogenisation technique with 0.1 %, 0.3 % or 0.6 % of the PEGylated phospholipid. A droplet size of approximately 100 nm and polydispersity index below 0.25 indicated suitability for parenteral application. EPR analysis showed that PEG2000-DSPE had a stabilising effect on selected NEs, which was most pronounced in the part of the stabilising layer closest to the aqueous phase. To confirm these results, protein interaction studies were carried out using dynamic light scattering, UV–Vis spectroscopy, atomic force microscopy and release studies from protein-enriched media – bovine serum albumin (BSA) or foetal bovine serum (FBS) in phosphate-buffered saline. These analyses confirmed that the addition of PEG2000-DSPE reduced protein binding to the droplets as a function of concentration, with 0.3 % providing the best protection for the droplets. Our conclusions from the EPR spectroscopy study demonstrate the usefulness of EPR in determining the optimal concentrations of PEGylating agents for surface coverage and its usefulness in the formulation development phase.
PB  - Elsevier B.V.
T2  - Journal of Molecular Liquids
T1  - Evaluation of PEGylation efficacy of curcumin-loaded nanoemulsions using complementary methods to assess protein interactions and physicochemical properties
VL  - 404
DO  - 10.1016/j.molliq.2024.124888
ER  - 

@article{
author = "Đoković, Jelena and Demisli, Sortiria and Savić, Sanela M. and Savić, Saša R. and Randjelović, Danijela V. and Marković, Bojan and Pantelić, Ivana and Mitrović, Jelena and Stanković, Tijana and Papadimitrou, Vassiliki and Xenakis, Aristotelis and Savić, Snežana",
year = "2024",
abstract = "Nanoemulsions (NEs) are frequently used in the food, cosmetics and pharmaceutical industries to deliver nutraceuticals, pharmaceutical or cosmetic active ingredients. When administering NEs parenterally, various stabilisers are added to prevent rapid plasma clearance and to successfully deliver the active ingredient to the target site. For this purpose, PEGylation is often used to prolong the circulation time of the droplets. However, the problem is to determine the optimal concentration of the PEGylating agent – the PEGylation efficacy – that ensures adequate surface protection. This is a particular challenge when the active ingredient is incorporated into the stabilising layer, where any changes could disrupt the stability of the droplet. For this reason, we aimed to determine the optimal concentration of PEG2000-DSPE for surface protection of curcumin-loaded NEs for parenteral administration using electron paramagnetic resonance (EPR) spectroscopy. NEs were prepared using the high pressure homogenisation technique with 0.1 %, 0.3 % or 0.6 % of the PEGylated phospholipid. A droplet size of approximately 100 nm and polydispersity index below 0.25 indicated suitability for parenteral application. EPR analysis showed that PEG2000-DSPE had a stabilising effect on selected NEs, which was most pronounced in the part of the stabilising layer closest to the aqueous phase. To confirm these results, protein interaction studies were carried out using dynamic light scattering, UV–Vis spectroscopy, atomic force microscopy and release studies from protein-enriched media – bovine serum albumin (BSA) or foetal bovine serum (FBS) in phosphate-buffered saline. These analyses confirmed that the addition of PEG2000-DSPE reduced protein binding to the droplets as a function of concentration, with 0.3 % providing the best protection for the droplets. Our conclusions from the EPR spectroscopy study demonstrate the usefulness of EPR in determining the optimal concentrations of PEGylating agents for surface coverage and its usefulness in the formulation development phase.",
publisher = "Elsevier B.V.",
journal = "Journal of Molecular Liquids",
title = "Evaluation of PEGylation efficacy of curcumin-loaded nanoemulsions using complementary methods to assess protein interactions and physicochemical properties",
volume = "404",
doi = "10.1016/j.molliq.2024.124888"
}

Đoković, J., Demisli, S., Savić, S. M., Savić, S. R., Randjelović, D. V., Marković, B., Pantelić, I., Mitrović, J., Stanković, T., Papadimitrou, V., Xenakis, A.,& Savić, S.. (2024). Evaluation of PEGylation efficacy of curcumin-loaded nanoemulsions using complementary methods to assess protein interactions and physicochemical properties. in Journal of Molecular Liquids
Elsevier B.V.., 404.
https://doi.org/10.1016/j.molliq.2024.124888

Đoković J, Demisli S, Savić SM, Savić SR, Randjelović DV, Marković B, Pantelić I, Mitrović J, Stanković T, Papadimitrou V, Xenakis A, Savić S. Evaluation of PEGylation efficacy of curcumin-loaded nanoemulsions using complementary methods to assess protein interactions and physicochemical properties. in Journal of Molecular Liquids. 2024;404.
doi:10.1016/j.molliq.2024.124888 .

Đoković, Jelena, Demisli, Sortiria, Savić, Sanela M., Savić, Saša R., Randjelović, Danijela V., Marković, Bojan, Pantelić, Ivana, Mitrović, Jelena, Stanković, Tijana, Papadimitrou, Vassiliki, Xenakis, Aristotelis, Savić, Snežana, "Evaluation of PEGylation efficacy of curcumin-loaded nanoemulsions using complementary methods to assess protein interactions and physicochemical properties" in Journal of Molecular Liquids, 404 (2024),
https://doi.org/10.1016/j.molliq.2024.124888 . .

TY  - JOUR
AU  - Đorđević, Sanela
AU  - Cekić, Nebojša
AU  - Savić, Miroslav
AU  - Isailović, Tanja
AU  - Ranđelović, Danijela
AU  - Marković, Bojan
AU  - Savić, Saša R.
AU  - Timić-Stamenić, Tamara
AU  - Daniels, Rolf
AU  - Savić, Snežana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2346
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 Science BV, Amsterdam
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 = "Đorđević, Sanela and Cekić, Nebojša and Savić, Miroslav and Isailović, Tanja and Ranđelović, Danijela and Marković, Bojan and Savić, Saša R. and Timić-Stamenić, Tamara and Daniels, Rolf and Savić, Snežana",
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 Science BV, Amsterdam",
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"
}

Đorđević, S., Cekić, N., Savić, M., Isailović, T., Ranđelović, D., Marković, B., Savić, S. R., Timić-Stamenić, T., Daniels, R.,& Savić, S.. (2015). Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation. in International Journal of Pharmaceutics
Elsevier Science BV, Amsterdam., 493(1-2), 40-54.
https://doi.org/10.1016/j.ijpharm.2015.07.007

Đorđević S, Cekić N, Savić M, Isailović T, Ranđelović D, Marković B, Savić SR, Timić-Stamenić T, Daniels R, Savić S. 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 .

Đorđević, Sanela, Cekić, Nebojša, Savić, Miroslav, Isailović, Tanja, Ranđelović, Danijela, Marković, Bojan, Savić, Saša R., Timić-Stamenić, Tamara, Daniels, Rolf, Savić, Snežana, "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  - Cekić, Nebojša
AU  - Đorđević, Sanela
AU  - Savić, Saša R.
AU  - Savić, Snežana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2351
AB  - Using the experimental design methodology, we have developed and characterized nanoemulsions for a parenteral delivery using diazepam as a model drug. The formulations containing 20 or 30% (w/w) of medium chain triglycerides or the mixture of medium chain triglycerides and soybean oil as the oil phase, soybean lecithin and polysorbate 80 as emulsifiers, and a phosphate buffer solution as the aqueous phase were prepared by cold high pressure homogenization. The obtained nanoemulsions were evaluated in terms of droplet size, size distribution, surface charge, drug-vehicle interactions and physical stability. To evaluate the effects of the oil phase type, oil content and drug presence, as well as their interactions on critical quality attributes of nanoemulsions, a three-factor two-level full factorial design was applied. After the preparation, all nanoemulsions revealed small spherical droplets in the range 170-210 nm, with the narrow droplet size distribution ( lt  0.15) and the surface charge about -60 mV. The experimental design results indicated that not only factors alone (oil type, oil content, presence of drug), but their interactions also had a significant effect on the nanoemulsion droplet size, polydispersity index, and zeta potential. During two months of storage at 25°C, all nanoemulsions formulated with the medium chain triglycerides-soybean oil mixture (4:1, w/w) remained physically stable, without considerable changes in monitored parameters. Physicochemical characteristics and stability of these nanoemulsions demonstrated their suitability for parenteral drug delivery.
AB  - Cilj ovog rada bio je da se primenom metodologije eksperimentalnog dizajna razviju parenteralne nanoemulzije sa diazepamom kao model lekovitom supstancom i da se sprovede njihova sveobuhvatna fizičkohemijska karakterizacija. Metodom homogenizacije pod visokim pritiskom na sobnoj temperaturi izrađene su placebo i nanoemulzije sa lekom, stabilizovane smešom lecitina i polisorbata 80, variranjem udela i vrste uljane faze - 20 i 30% (m/m) triglicerida srednje dužine lanca ili smeše triglicerida srednje dužine lanca i sojinog ulja u odnosu 4:1. Dobijene nanoemulzije okarakterisane su u pogledu veličine i raspodele veličina kapi, površinskog naelektrisanja, interakcija lek-nosač i fizičke stabilnosti. U cilju procene istovremenog uticaja vrste uljane faze, udela ulja i prisustva leka, kao i njihovih interakcija, na kritične atribute kvaliteta nanoemulzija, primenjen je pun faktorski dizajn sa tri faktora na dva nivoa. Nakon izrade, sve formulacije nanoemulzija imale su malu veličinu kapi u opsegu 170-210 nm, sa veoma uskom raspodelom veličina (ispod 0,15) i površinskim naelektrisanjem oko -60 mV. Rezultati eksperimentalnog dizajna pokazali su da ne samo pojedinačni faktori (vrsta ulja, koncentracija ulja, prisustvo leka), nego i njihove interakcije, značajno utiču na veličinu kapi, indeks polidisperznosti i zeta potencijal ispitivanih nanoemulzija. Tokom 2 meseca čuvanja na 25°C, sve nanoemulzije formulisane sa smešom triglicerida srednje dužine lanca i sojinog ulja kao uljanom fazom bile su fizički stabilne, bez značajnih promena u praćenim parametrima. Fizičkohemijske karakteristike i stabilnost navedenih nanoemulzija ukazuju da one mogu biti potencijalni nosači za parenteralnu isporuku lekovitih supstanci.
PB  - Univerzitet u Nišu - Tehnološki fakultet, Leskovac
T2  - Advanced Technologies
T1  - A full factorial design in the formulation of diazepam parenteral nanoemulsions: Physicochemical characterization and stability evaluation
T1  - Pun faktorski dizajn u formulaciji parenteralnih nanoemulzija sa diazepamom - fizičkohemijska karakterizacija i procena stabilnosti
VL  - 4
IS  - 1
SP  - 69
EP  - 77
DO  - 10.5937/savteh1501069C
ER  - 

@article{
author = "Cekić, Nebojša and Đorđević, Sanela and Savić, Saša R. and Savić, Snežana",
year = "2015",
abstract = "Using the experimental design methodology, we have developed and characterized nanoemulsions for a parenteral delivery using diazepam as a model drug. The formulations containing 20 or 30% (w/w) of medium chain triglycerides or the mixture of medium chain triglycerides and soybean oil as the oil phase, soybean lecithin and polysorbate 80 as emulsifiers, and a phosphate buffer solution as the aqueous phase were prepared by cold high pressure homogenization. The obtained nanoemulsions were evaluated in terms of droplet size, size distribution, surface charge, drug-vehicle interactions and physical stability. To evaluate the effects of the oil phase type, oil content and drug presence, as well as their interactions on critical quality attributes of nanoemulsions, a three-factor two-level full factorial design was applied. After the preparation, all nanoemulsions revealed small spherical droplets in the range 170-210 nm, with the narrow droplet size distribution ( lt  0.15) and the surface charge about -60 mV. The experimental design results indicated that not only factors alone (oil type, oil content, presence of drug), but their interactions also had a significant effect on the nanoemulsion droplet size, polydispersity index, and zeta potential. During two months of storage at 25°C, all nanoemulsions formulated with the medium chain triglycerides-soybean oil mixture (4:1, w/w) remained physically stable, without considerable changes in monitored parameters. Physicochemical characteristics and stability of these nanoemulsions demonstrated their suitability for parenteral drug delivery., Cilj ovog rada bio je da se primenom metodologije eksperimentalnog dizajna razviju parenteralne nanoemulzije sa diazepamom kao model lekovitom supstancom i da se sprovede njihova sveobuhvatna fizičkohemijska karakterizacija. Metodom homogenizacije pod visokim pritiskom na sobnoj temperaturi izrađene su placebo i nanoemulzije sa lekom, stabilizovane smešom lecitina i polisorbata 80, variranjem udela i vrste uljane faze - 20 i 30% (m/m) triglicerida srednje dužine lanca ili smeše triglicerida srednje dužine lanca i sojinog ulja u odnosu 4:1. Dobijene nanoemulzije okarakterisane su u pogledu veličine i raspodele veličina kapi, površinskog naelektrisanja, interakcija lek-nosač i fizičke stabilnosti. U cilju procene istovremenog uticaja vrste uljane faze, udela ulja i prisustva leka, kao i njihovih interakcija, na kritične atribute kvaliteta nanoemulzija, primenjen je pun faktorski dizajn sa tri faktora na dva nivoa. Nakon izrade, sve formulacije nanoemulzija imale su malu veličinu kapi u opsegu 170-210 nm, sa veoma uskom raspodelom veličina (ispod 0,15) i površinskim naelektrisanjem oko -60 mV. Rezultati eksperimentalnog dizajna pokazali su da ne samo pojedinačni faktori (vrsta ulja, koncentracija ulja, prisustvo leka), nego i njihove interakcije, značajno utiču na veličinu kapi, indeks polidisperznosti i zeta potencijal ispitivanih nanoemulzija. Tokom 2 meseca čuvanja na 25°C, sve nanoemulzije formulisane sa smešom triglicerida srednje dužine lanca i sojinog ulja kao uljanom fazom bile su fizički stabilne, bez značajnih promena u praćenim parametrima. Fizičkohemijske karakteristike i stabilnost navedenih nanoemulzija ukazuju da one mogu biti potencijalni nosači za parenteralnu isporuku lekovitih supstanci.",
publisher = "Univerzitet u Nišu - Tehnološki fakultet, Leskovac",
journal = "Advanced Technologies",
title = "A full factorial design in the formulation of diazepam parenteral nanoemulsions: Physicochemical characterization and stability evaluation, Pun faktorski dizajn u formulaciji parenteralnih nanoemulzija sa diazepamom - fizičkohemijska karakterizacija i procena stabilnosti",
volume = "4",
number = "1",
pages = "69-77",
doi = "10.5937/savteh1501069C"
}

Cekić, N., Đorđević, S., Savić, S. R.,& Savić, S.. (2015). A full factorial design in the formulation of diazepam parenteral nanoemulsions: Physicochemical characterization and stability evaluation. in Advanced Technologies
Univerzitet u Nišu - Tehnološki fakultet, Leskovac., 4(1), 69-77.
https://doi.org/10.5937/savteh1501069C

Cekić N, Đorđević S, Savić SR, Savić S. A full factorial design in the formulation of diazepam parenteral nanoemulsions: Physicochemical characterization and stability evaluation. in Advanced Technologies. 2015;4(1):69-77.
doi:10.5937/savteh1501069C .

Cekić, Nebojša, Đorđević, Sanela, Savić, Saša R., Savić, Snežana, "A full factorial design in the formulation of diazepam parenteral nanoemulsions: Physicochemical characterization and stability evaluation" in Advanced Technologies, 4, no. 1 (2015):69-77,
https://doi.org/10.5937/savteh1501069C . .