TY  - JOUR
AU  - Demisli, Sotiria
AU  - Galani, Eleni
AU  - Goulielmaki, Maria
AU  - Kyrilis, Fotios
AU  - Ilić, Tanja
AU  - Hamdi, Farzad
AU  - Crevar, Milkica
AU  - Kastritis, Panagiotis
AU  - Pletsa, Vasiliki
AU  - Nallet, Frédéric
AU  - Savić, Snežana
AU  - Xenakis, Aristotelis
AU  - Papadimitriou, Vassiliki
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4384
AB  - Hypothesis: Lipophilic cannabidiol can be solubilized in oil-in water nanoemulsions, which can then be impregnated into chitosan hydrogels forming another colloidal system that will facilitate cannabidiol's release. The delivery from both systems was compared, alongside structural and biological studies, to clarify the effect of the two carriers' structure on the release and toxicity of the systems. Experiments: Oil-in-water nanoemulsions (NEs) and the respective nanoemulsion-filled chitosan hydrogels (NE/HGs) were formulated as carriers of cannabidiol (CBD). Size, polydispersity and stability of the NEs were evaluated and then membrane dynamics, shape and structure of both systems were investigated with EPR spin probing, SAXS and microscopy. Biocompatibility of the colloidal delivery systems was evaluated through cytotoxicity tests over normal human skin fibroblasts. An ex vivo permeation protocol using porcine ear skin was implemented to assess the release of CBD and its penetration through the skin. Findings: Incorporation of the NEs in chitosan hydrogels does not significantly affect their structural properties as evidenced through SAXS, EPR and confocal microscopy. These findings indicate the successful development of a novel nanocarrier that preserves the NE structure with the CBD remaining encapsulated in the oil core while providing new rheological properties advantageous over NEs. Moreover, NE/HGs proved to be more efficient as a carrier for the release of CBD. Cell viability assessment revealed high biocompatibility of the proposed colloids.
PB  - Academic Press Inc.
T2  - Journal of Colloid and Interface Science
T1  - Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study
VL  - 634
SP  - 300
EP  - 313
DO  - 10.1016/j.jcis.2022.12.036
ER  - 

@article{
author = "Demisli, Sotiria and Galani, Eleni and Goulielmaki, Maria and Kyrilis, Fotios and Ilić, Tanja and Hamdi, Farzad and Crevar, Milkica and Kastritis, Panagiotis and Pletsa, Vasiliki and Nallet, Frédéric and Savić, Snežana and Xenakis, Aristotelis and Papadimitriou, Vassiliki",
year = "2023",
abstract = "Hypothesis: Lipophilic cannabidiol can be solubilized in oil-in water nanoemulsions, which can then be impregnated into chitosan hydrogels forming another colloidal system that will facilitate cannabidiol's release. The delivery from both systems was compared, alongside structural and biological studies, to clarify the effect of the two carriers' structure on the release and toxicity of the systems. Experiments: Oil-in-water nanoemulsions (NEs) and the respective nanoemulsion-filled chitosan hydrogels (NE/HGs) were formulated as carriers of cannabidiol (CBD). Size, polydispersity and stability of the NEs were evaluated and then membrane dynamics, shape and structure of both systems were investigated with EPR spin probing, SAXS and microscopy. Biocompatibility of the colloidal delivery systems was evaluated through cytotoxicity tests over normal human skin fibroblasts. An ex vivo permeation protocol using porcine ear skin was implemented to assess the release of CBD and its penetration through the skin. Findings: Incorporation of the NEs in chitosan hydrogels does not significantly affect their structural properties as evidenced through SAXS, EPR and confocal microscopy. These findings indicate the successful development of a novel nanocarrier that preserves the NE structure with the CBD remaining encapsulated in the oil core while providing new rheological properties advantageous over NEs. Moreover, NE/HGs proved to be more efficient as a carrier for the release of CBD. Cell viability assessment revealed high biocompatibility of the proposed colloids.",
publisher = "Academic Press Inc.",
journal = "Journal of Colloid and Interface Science",
title = "Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study",
volume = "634",
pages = "300-313",
doi = "10.1016/j.jcis.2022.12.036"
}

Demisli, S., Galani, E., Goulielmaki, M., Kyrilis, F., Ilić, T., Hamdi, F., Crevar, M., Kastritis, P., Pletsa, V., Nallet, F., Savić, S., Xenakis, A.,& Papadimitriou, V.. (2023). Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study. in Journal of Colloid and Interface Science
Academic Press Inc.., 634, 300-313.
https://doi.org/10.1016/j.jcis.2022.12.036

Demisli S, Galani E, Goulielmaki M, Kyrilis F, Ilić T, Hamdi F, Crevar M, Kastritis P, Pletsa V, Nallet F, Savić S, Xenakis A, Papadimitriou V. Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study. in Journal of Colloid and Interface Science. 2023;634:300-313.
doi:10.1016/j.jcis.2022.12.036 .

Demisli, Sotiria, Galani, Eleni, Goulielmaki, Maria, Kyrilis, Fotios, Ilić, Tanja, Hamdi, Farzad, Crevar, Milkica, Kastritis, Panagiotis, Pletsa, Vasiliki, Nallet, Frédéric, Savić, Snežana, Xenakis, Aristotelis, Papadimitriou, Vassiliki, "Encapsulation of cannabidiol in oil-in-water nanoemulsions and nanoemulsion-filled hydrogels: A structure and biological assessment study" in Journal of Colloid and Interface Science, 634 (2023):300-313,
https://doi.org/10.1016/j.jcis.2022.12.036 . .

TY  - CONF
AU  - Đoković, Jelena
AU  - Demisli, Sotiria
AU  - Papadimitriou, Vassiliki
AU  - Savić, Snežana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4572
AB  - INTRODUCTION
Nanoemulsions (NEs) offer a flexible platform for drug delivery via several administration routes. Rapid plasma clearance brought on by interactions with plasma proteins and the activation of the mononuclear phagocytic system is the greatest challenge NEs face after parenteral administration. PEGylation, or adding PEGylated phospholipids to the stabilizing layer of the NEs, is one method for ensuring that droplets circulate for a longer period of time. It is crucial to select the optimum concentration of the PEGylated in order to maintain the necessary physicochemical properties of NEs while providing appropriate surface coverage with the PEG chains. Curcumin is a model active that has been found to be localized in the stabilizing layer of NEs (1-3) and offers a wide range of potential health benefits, but due to its short plasma half-life, new strategies for enhancing bioavailability are required. The purpose of this study is to investigate the effects of various PEGylated phospholipid (PEG2000-DSPE) concentrations on the structural properties of NEs with an active placed in the stabilizing layer.
PREPARATION OF NANOEMULSIONS
All the NEs were prepared using the high pressure homogenization technique. The aqueous phase (glycerol, polysorbate 80, sodium oleate and highly purified water) was added to the oil phase (soybean oil, medium chain triglycerides, soybean lecithin, buthylhydroxytoluene, curcumin and 0.1%/0.3%/0.6% PEG2000-DSPE) and mixed at 11000rpm for 1 min on rotor stator homogenizer (IKA Ultra-Turrax T25 digital, IKA-Werke GmbH & Co. KG, Staufen, Germany), and then further processed at 800 bar for 10 discontinued cycles (EmulsiFlex-C3, Avestin Inc., Ottawa,ON, Canada) to obtain CS21, CS23 and CS26 formulations.
NANOEMULSION DROPLET SIZE
The droplet size was assessed through the dynamic light scattering method and presented as mean droplet size (Z-ave) and polydispersity index (PDI), after diluting the NEs 1:500 (v/v) in highly purified water.
ELECTRON PARAMAGNETIC RESONANCE (EPR) SPECTROSCOPY
For this study three amphiphilic fatty acid derivatives labeled at different positions of the aliphatic chain (5-DSA, 12-DSA and 16-DSA) were used to probe the dynamics of the membrane at different depths. Stock solutions of the spin probes were prepared in absolute ethanol at 1mM concentration. Subsequently, 15 µl of the stock solutions were evaporated and then incubated with 1 ml of the NE sample in final concentration of 0.015 mM. The resulting spectra was analyzed in terms of rotational correlation time (τR), order parameter (S) and isotropic hyperfine constant (αN).
RESULTS AND DISCUSION
All of the formulations had average droplet sizes between 95 and 103 nm and PDI values under 0.25, which indicated that they were suitable for parenteral administration.
The results of the EPR investigation showed that the stabilizing layer changed as the amount of PEGylated phospholipids increased, indicating that the PEGylation threshold has not yet been reached in the stabilizing layer.
The EPR research also showed that the 5-DSA spin probe's spectra were significantly affected by the addition of various PEGylated phospholipid concentrations (Figure 1). This indicates that the portion of the stabilizing layer nearest to the aqueous phase was the one most affected by the increase in the PEGylated phospholipid concentration. Table 1 provides the calculated values for the spectrum parameters. The mobility of the spin-probe and the time it takes for the spin-probe to make a full rotation is reflected in the τR parameter, which was changed the most, compared to the other parameters, by the variations in the PEGylated phospholipid content. A formulation with the most rigid stabilizing layer had the largest τR values, which, in this instance, was the formulation with 0.1% PEG2000-DSPE. It's interesting to note that the addition of PEGylated phospholipid had the opposite effect of strengthening the stabilizing layer. Further PEG2000-DSPE addition appeared to result in nanoemulsions with a less rigid stabilizing layer, possibly indicating that larger concentrations of the PEGylating agent lead to interface destabilization. The interactions between the curcumin, a symmetrical molecule with two aromatic ring systems and a bent conformation located in the stabilizing layer and the extra stabilizer are likely responsible for this.
The other two spin probes (12-DSA and 16-DSA) provide information about the stabilizing layer located closer to the oil core. Based on the data provided in Table 1 it can be inferred that the PEGylation mostly affects the stabilizing layer's areas closest to the aqueous interface, leaving the parts closer to the oil core largely not impacted.
CONCLUSION
This study demonstrates that one of the key elements in assessing how PEGylation affects the NE system is the active's localization. To pick the concentration of the PEGylated phospholipid that will offer the best surface coverage without compromising the integrity of the interface, additional considerations must be addressed in the event of an active situated in the stabilizing layer. In this instance, it may be hypothesized that the lowest PEG2000-DSPE concentration of 0.1%, CS21, will produce NEs that can slow down curcumin release the most compared to the other two formulations. Additionally, given that further addition of the PEGylated phospholipid causes the formation of less rigid stabilizing layer, further inquiries should be made to see the impact of these changes on the interactions with plasma proteins and biological fate of the droplets upon administration.
C3  - 4th European Conference on Pharmaceutics, 20 - 21 March 2023, Marseille, France
T1  - Structural analysis of PEGylated nanoemulsions using EPR spectroscopy – the impact of an active compound incorporated in stabilizing layer
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4572
ER  - 

@conference{
author = "Đoković, Jelena and Demisli, Sotiria and Papadimitriou, Vassiliki and Savić, Snežana",
year = "2023",
abstract = "INTRODUCTION
Nanoemulsions (NEs) offer a flexible platform for drug delivery via several administration routes. Rapid plasma clearance brought on by interactions with plasma proteins and the activation of the mononuclear phagocytic system is the greatest challenge NEs face after parenteral administration. PEGylation, or adding PEGylated phospholipids to the stabilizing layer of the NEs, is one method for ensuring that droplets circulate for a longer period of time. It is crucial to select the optimum concentration of the PEGylated in order to maintain the necessary physicochemical properties of NEs while providing appropriate surface coverage with the PEG chains. Curcumin is a model active that has been found to be localized in the stabilizing layer of NEs (1-3) and offers a wide range of potential health benefits, but due to its short plasma half-life, new strategies for enhancing bioavailability are required. The purpose of this study is to investigate the effects of various PEGylated phospholipid (PEG2000-DSPE) concentrations on the structural properties of NEs with an active placed in the stabilizing layer.
PREPARATION OF NANOEMULSIONS
All the NEs were prepared using the high pressure homogenization technique. The aqueous phase (glycerol, polysorbate 80, sodium oleate and highly purified water) was added to the oil phase (soybean oil, medium chain triglycerides, soybean lecithin, buthylhydroxytoluene, curcumin and 0.1%/0.3%/0.6% PEG2000-DSPE) and mixed at 11000rpm for 1 min on rotor stator homogenizer (IKA Ultra-Turrax T25 digital, IKA-Werke GmbH & Co. KG, Staufen, Germany), and then further processed at 800 bar for 10 discontinued cycles (EmulsiFlex-C3, Avestin Inc., Ottawa,ON, Canada) to obtain CS21, CS23 and CS26 formulations.
NANOEMULSION DROPLET SIZE
The droplet size was assessed through the dynamic light scattering method and presented as mean droplet size (Z-ave) and polydispersity index (PDI), after diluting the NEs 1:500 (v/v) in highly purified water.
ELECTRON PARAMAGNETIC RESONANCE (EPR) SPECTROSCOPY
For this study three amphiphilic fatty acid derivatives labeled at different positions of the aliphatic chain (5-DSA, 12-DSA and 16-DSA) were used to probe the dynamics of the membrane at different depths. Stock solutions of the spin probes were prepared in absolute ethanol at 1mM concentration. Subsequently, 15 µl of the stock solutions were evaporated and then incubated with 1 ml of the NE sample in final concentration of 0.015 mM. The resulting spectra was analyzed in terms of rotational correlation time (τR), order parameter (S) and isotropic hyperfine constant (αN).
RESULTS AND DISCUSION
All of the formulations had average droplet sizes between 95 and 103 nm and PDI values under 0.25, which indicated that they were suitable for parenteral administration.
The results of the EPR investigation showed that the stabilizing layer changed as the amount of PEGylated phospholipids increased, indicating that the PEGylation threshold has not yet been reached in the stabilizing layer.
The EPR research also showed that the 5-DSA spin probe's spectra were significantly affected by the addition of various PEGylated phospholipid concentrations (Figure 1). This indicates that the portion of the stabilizing layer nearest to the aqueous phase was the one most affected by the increase in the PEGylated phospholipid concentration. Table 1 provides the calculated values for the spectrum parameters. The mobility of the spin-probe and the time it takes for the spin-probe to make a full rotation is reflected in the τR parameter, which was changed the most, compared to the other parameters, by the variations in the PEGylated phospholipid content. A formulation with the most rigid stabilizing layer had the largest τR values, which, in this instance, was the formulation with 0.1% PEG2000-DSPE. It's interesting to note that the addition of PEGylated phospholipid had the opposite effect of strengthening the stabilizing layer. Further PEG2000-DSPE addition appeared to result in nanoemulsions with a less rigid stabilizing layer, possibly indicating that larger concentrations of the PEGylating agent lead to interface destabilization. The interactions between the curcumin, a symmetrical molecule with two aromatic ring systems and a bent conformation located in the stabilizing layer and the extra stabilizer are likely responsible for this.
The other two spin probes (12-DSA and 16-DSA) provide information about the stabilizing layer located closer to the oil core. Based on the data provided in Table 1 it can be inferred that the PEGylation mostly affects the stabilizing layer's areas closest to the aqueous interface, leaving the parts closer to the oil core largely not impacted.
CONCLUSION
This study demonstrates that one of the key elements in assessing how PEGylation affects the NE system is the active's localization. To pick the concentration of the PEGylated phospholipid that will offer the best surface coverage without compromising the integrity of the interface, additional considerations must be addressed in the event of an active situated in the stabilizing layer. In this instance, it may be hypothesized that the lowest PEG2000-DSPE concentration of 0.1%, CS21, will produce NEs that can slow down curcumin release the most compared to the other two formulations. Additionally, given that further addition of the PEGylated phospholipid causes the formation of less rigid stabilizing layer, further inquiries should be made to see the impact of these changes on the interactions with plasma proteins and biological fate of the droplets upon administration.",
journal = "4th European Conference on Pharmaceutics, 20 - 21 March 2023, Marseille, France",
title = "Structural analysis of PEGylated nanoemulsions using EPR spectroscopy – the impact of an active compound incorporated in stabilizing layer",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4572"
}

Đoković, J., Demisli, S., Papadimitriou, V.,& Savić, S.. (2023). Structural analysis of PEGylated nanoemulsions using EPR spectroscopy – the impact of an active compound incorporated in stabilizing layer. in 4th European Conference on Pharmaceutics, 20 - 21 March 2023, Marseille, France.
https://hdl.handle.net/21.15107/rcub_farfar_4572

Đoković J, Demisli S, Papadimitriou V, Savić S. Structural analysis of PEGylated nanoemulsions using EPR spectroscopy – the impact of an active compound incorporated in stabilizing layer. in 4th European Conference on Pharmaceutics, 20 - 21 March 2023, Marseille, France. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_4572 .

Đoković, Jelena, Demisli, Sotiria, Papadimitriou, Vassiliki, Savić, Snežana, "Structural analysis of PEGylated nanoemulsions using EPR spectroscopy – the impact of an active compound incorporated in stabilizing layer" in 4th European Conference on Pharmaceutics, 20 - 21 March 2023, Marseille, France (2023),
https://hdl.handle.net/21.15107/rcub_farfar_4572 .

TY  - CONF
AU  - Đoković, Jelena
AU  - Demisli, Sotiria
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Savić, Snežana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4284
AB  - ANALYZING THE IMPACT OF THE OIL PHASE SELECTION AND CURCUMIN
PRESENCE ON THE NANOEMULSION STABILIZING LAYER USING ELECTRON
PARAMAGNETIC RESONANCE SPECTROSCOPY
Jelena	Đoković1*, Sotiria Demisli2, Vassiliki Papadimitriou2,		
Aristotelis Xenakis2, Snežana Savić1
1University of Belgrade – Faculty of Pharmacy, Department of Pharmaceutical
Technology and Cosmetology, Belgrade, Serbia
2National Hellenic Research Foundation – Institute of Chemical Biology, Athens,
Greece
*jelenadj@pharmacy.bg.ac.rs
The stabilizing layer of nanoemulsions impacts their stability and destiny upon in vivo
administration (1). The aim of this work was to gain information about the dynamics of the
surfactants’ monolayer when different oils (soybean / fish) were used, and obtain data
regarding the localization of curcumin (2), an active compound with many potential health
benefits, using electron paramagnetic resonance (EPR) spectroscopy. Formulations were
analysed using EPR technique with three different spin probes: 5-, 12- and 16-doxyl stearic
acid (DSA), to investigate membrane dynamics at different depths. The results indicated that
the oil type played a crucial role, not only on the structure, but also in the localization of the
bioactive compound. The addition of curcumin changed the rotational correlation time (τR)
values, most notably for 5-DSA, both in soybean oil and fish oil nanoemulsions, indicating its
localization in the stabilizing layer, but with opposite effects. In the soybean oil
nanoemulsion the addition of curcumin increased spin probe mobility, with τR decreasing
from 2.18±0.60 ns to 1.66±0.61 ns, indicating a less rigid stabilizing structure, while in the
fish oil formulations it resulted in a more rigid structure reflected in τR increase from
1.19±0.10 ns to 2.96±0.81 ns and 1.63±0.13 ns to 2.27±0.19 ns, for 5-DSA and 12-DSA,
respectively. This study concluded that the curcumin is located in the stabilizing layer of
nanoemulsions, but its impact on stabilizing layer structure depended on the oil phase
selection, with particular stabilizing effects on fish oil nanoemulsions.
References
1. Nikolic, I. et al. Curcumin-loaded low‐energy nanoemulsions: Linking EPR spectroscopy‐
analysed microstructure and antioxidant potential with in vitro evaluated biological activity.
J. Mol. Liq. 2020, 301, 112479.
2. Griffith, O.H. and Jost, P.C. Lipid Spin Labels in Biological Membrane. In Spin Labeling,
Theory and Applications; Berliner, L.J., Eds.; Academic Press: New York, NY, USA, 1976;
pp 454–484
Acknowledgements
This research was funded by the MESDT, Republic of Serbia through Grant Agreement
with University of Belgrade – Faculty of Pharmacy No: 451-03-68/2022-14/200161 and
supported by the Science Fund of the Republic of Serbia, GRANT No 7749108, Neuroimmune
aspects of mood, anxiety and cognitive effects of leads/drug candidates acting at GABAA
and/or sigma‐2 receptors: In vitro/in vivo delineation by nano‐	 and hiPSC‐based platform -
NanoCellEmоCog
C3  - 8. Kongres farmaceuta Srbije; 12.-15. oktobar, Beograd, Srbija
T1  - Analyzing the impact of the oil phase selection and curcumin presence on the nanoemulsion stabilizing layer using electron paramagnetic resonance spectroscopy
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4284
ER  - 

@conference{
author = "Đoković, Jelena and Demisli, Sotiria and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Savić, Snežana",
year = "2022",
abstract = "ANALYZING THE IMPACT OF THE OIL PHASE SELECTION AND CURCUMIN
PRESENCE ON THE NANOEMULSION STABILIZING LAYER USING ELECTRON
PARAMAGNETIC RESONANCE SPECTROSCOPY
Jelena	Đoković1*, Sotiria Demisli2, Vassiliki Papadimitriou2,		
Aristotelis Xenakis2, Snežana Savić1
1University of Belgrade – Faculty of Pharmacy, Department of Pharmaceutical
Technology and Cosmetology, Belgrade, Serbia
2National Hellenic Research Foundation – Institute of Chemical Biology, Athens,
Greece
*jelenadj@pharmacy.bg.ac.rs
The stabilizing layer of nanoemulsions impacts their stability and destiny upon in vivo
administration (1). The aim of this work was to gain information about the dynamics of the
surfactants’ monolayer when different oils (soybean / fish) were used, and obtain data
regarding the localization of curcumin (2), an active compound with many potential health
benefits, using electron paramagnetic resonance (EPR) spectroscopy. Formulations were
analysed using EPR technique with three different spin probes: 5-, 12- and 16-doxyl stearic
acid (DSA), to investigate membrane dynamics at different depths. The results indicated that
the oil type played a crucial role, not only on the structure, but also in the localization of the
bioactive compound. The addition of curcumin changed the rotational correlation time (τR)
values, most notably for 5-DSA, both in soybean oil and fish oil nanoemulsions, indicating its
localization in the stabilizing layer, but with opposite effects. In the soybean oil
nanoemulsion the addition of curcumin increased spin probe mobility, with τR decreasing
from 2.18±0.60 ns to 1.66±0.61 ns, indicating a less rigid stabilizing structure, while in the
fish oil formulations it resulted in a more rigid structure reflected in τR increase from
1.19±0.10 ns to 2.96±0.81 ns and 1.63±0.13 ns to 2.27±0.19 ns, for 5-DSA and 12-DSA,
respectively. This study concluded that the curcumin is located in the stabilizing layer of
nanoemulsions, but its impact on stabilizing layer structure depended on the oil phase
selection, with particular stabilizing effects on fish oil nanoemulsions.
References
1. Nikolic, I. et al. Curcumin-loaded low‐energy nanoemulsions: Linking EPR spectroscopy‐
analysed microstructure and antioxidant potential with in vitro evaluated biological activity.
J. Mol. Liq. 2020, 301, 112479.
2. Griffith, O.H. and Jost, P.C. Lipid Spin Labels in Biological Membrane. In Spin Labeling,
Theory and Applications; Berliner, L.J., Eds.; Academic Press: New York, NY, USA, 1976;
pp 454–484
Acknowledgements
This research was funded by the MESDT, Republic of Serbia through Grant Agreement
with University of Belgrade – Faculty of Pharmacy No: 451-03-68/2022-14/200161 and
supported by the Science Fund of the Republic of Serbia, GRANT No 7749108, Neuroimmune
aspects of mood, anxiety and cognitive effects of leads/drug candidates acting at GABAA
and/or sigma‐2 receptors: In vitro/in vivo delineation by nano‐	 and hiPSC‐based platform -
NanoCellEmоCog",
journal = "8. Kongres farmaceuta Srbije; 12.-15. oktobar, Beograd, Srbija",
title = "Analyzing the impact of the oil phase selection and curcumin presence on the nanoemulsion stabilizing layer using electron paramagnetic resonance spectroscopy",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4284"
}

Đoković, J., Demisli, S., Papadimitriou, V., Xenakis, A.,& Savić, S.. (2022). Analyzing the impact of the oil phase selection and curcumin presence on the nanoemulsion stabilizing layer using electron paramagnetic resonance spectroscopy. in 8. Kongres farmaceuta Srbije; 12.-15. oktobar, Beograd, Srbija.
https://hdl.handle.net/21.15107/rcub_farfar_4284

Đoković J, Demisli S, Papadimitriou V, Xenakis A, Savić S. Analyzing the impact of the oil phase selection and curcumin presence on the nanoemulsion stabilizing layer using electron paramagnetic resonance spectroscopy. in 8. Kongres farmaceuta Srbije; 12.-15. oktobar, Beograd, Srbija. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4284 .

Đoković, Jelena, Demisli, Sotiria, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Savić, Snežana, "Analyzing the impact of the oil phase selection and curcumin presence on the nanoemulsion stabilizing layer using electron paramagnetic resonance spectroscopy" in 8. Kongres farmaceuta Srbije; 12.-15. oktobar, Beograd, Srbija (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4284 .

TY  - JOUR
AU  - Đoković, Jelena
AU  - Demisli, Sotiria
AU  - Savić, Sanela
AU  - Marković, Bojan
AU  - Cekić, Nebojša D.
AU  - Ranđelović, Danijela V.
AU  - Mitrović, Jelena
AU  - Lunter, Dominique Jasmin
AU  - Papadimitriou, Vassiliki
AU  - Xenakis, Aristotelis
AU  - Savić, Snežana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4265
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  - 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
DO  - 10.3390/pharmaceutics14081666
ER  - 

@article{
author = "Đoković, Jelena and Demisli, Sotiria and Savić, Sanela and Marković, Bojan and Cekić, Nebojša D. and Ranđelović, Danijela V. and Mitrović, Jelena and Lunter, Dominique Jasmin and Papadimitriou, Vassiliki and Xenakis, Aristotelis and Savić, Snežana",
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 = "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",
doi = "10.3390/pharmaceutics14081666"
}

Đoković, J., Demisli, S., Savić, S., Marković, B., Cekić, N. D., Ranđelović, D. V., Mitrović, J., Lunter, D. J., Papadimitriou, V., Xenakis, A.,& Savić, S.. (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
MDPI., 14(8).
https://doi.org/10.3390/pharmaceutics14081666

Đoković J, Demisli S, Savić S, Marković B, Cekić ND, Ranđelović DV, Mitrović J, Lunter DJ, Papadimitriou V, Xenakis A, Savić S. 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).
doi:10.3390/pharmaceutics14081666 .

Đoković, Jelena, Demisli, Sotiria, Savić, Sanela, Marković, Bojan, Cekić, Nebojša D., Ranđelović, Danijela V., Mitrović, Jelena, Lunter, Dominique Jasmin, Papadimitriou, Vassiliki, Xenakis, Aristotelis, Savić, Snežana, "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),
https://doi.org/10.3390/pharmaceutics14081666 . .