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Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment

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2020
IJP-D-19-02365R1_acc_byncnd.pdf (2.365Mb)
Authors
Jurišić Dukovski, Bisera
Juretić, Marina
Bračko, Danka
Randjelović, Danijela
Savić, Snežana
Crespo Moral, Mario
Diebold, Yolanda
Filipović-Grčić, Jelena
Pepić, Ivan
Lovrić, Jasmina
Article (Accepted Version)
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Abstract
Abstract: Inflammation plays a key role in dry eye disease (DED) affecting millions of people worldwide. Non-steroidal anti-inflammatory drugs (NSAIDs) can be used topically to act on the inflammatory component of DED, but their limited aqueous solubility raises formulation issues. The aim of this study was development and optimization of functional cationic nanoemulsions (NEs) for DED treatment, as a formulation approach to circumvent solubility problems, prolong drug residence at the ocular surface and stabilize the tear film. Ibuprofen was employed as the model NSAID, chitosan as the cationic agent, and lecithin as the anionic surfactant enabling chitosan incorporation. Moreover, lecithin is a mixture of phospholipids including phosphatidylcholine and phosphatidylethanolamine, two constituents of the natural tear film important for its stability. NEs were characterized in terms of droplet size, polydispersity index, zeta-potential, pH, viscosity, osmolarity, surface te...nsion, entrapment efficiency, stability, sterilizability and in vitro release. NEs mucoadhesive properties were tested rheologically after mixing with mucin dispersion. Biocompatibility was assessed employing 3D HCE-T cell-based model and ex vivo model using porcine corneas. The results of our study pointed out the NE formulation with 0.05 % (w/w) chitosan as the lead formulation with physicochemical properties adequate for ophthalmic application, mucoadhesive character and excellent biocompatibility.

Keywords:
dry eye disease / nanoemulsion / NSAID / chitosan / lecithin
Source:
International Journal of Pharmaceutics, 2020, 576, 118979-
Publisher:
  • Elsevier
Funding / projects:
  • Spanish Government Grant RTI2018-094071-B-C21 (MCIU/AEI/FEDER, UE) (YD and MC-M)
  • opical nanodelivery systems funded by the University of Zagreb (Z169)
  • “Modelling of the Pharmaceutical Spray Drying Process of the Emulsions in Laboratory and Pilot Scale” in collaboration with the industrial partner PLIVA Croatia Ltd.
Note:
  • This is the peer-reviewed version of the manuscript: Bisera Jurišić Dukovski et.al., Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment, International Journal of Pharmaceutics, 2020, 576, 118979, DOI: https://doi.org/10.1016/j.ijpharm.2019.118979
  • The published version: https://cer.ihtm.bg.ac.rs/handle/123456789/4012

DOI: 10.1016/j.ijpharm.2019.118979

ISSN: 0378-5173

PubMed: 31870964

WoS: 000512972500015

Scopus: 2-s2.0-85077471068
[ Google Scholar ]
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14
URI
https://cer.ihtm.bg.ac.rs/handle/123456789/4011
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
IHTM
TY  - JOUR
AU  - Jurišić Dukovski, Bisera
AU  - Juretić, Marina
AU  - Bračko, Danka
AU  - Randjelović, Danijela
AU  - Savić, Snežana
AU  - Crespo Moral, Mario
AU  - Diebold, Yolanda
AU  - Filipović-Grčić, Jelena
AU  - Pepić, Ivan
AU  - Lovrić, Jasmina
PY  - 2020
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/4011
AB  - Abstract: Inflammation plays a key role in dry eye disease (DED)
affecting millions of people worldwide. Non-steroidal anti-inflammatory
drugs (NSAIDs) can be used topically to act on the inflammatory component
of DED, but their limited aqueous solubility raises formulation issues.
The aim of this study was development and optimization of functional
cationic nanoemulsions (NEs) for DED treatment, as a formulation approach
to circumvent solubility problems, prolong drug residence at the ocular
surface and stabilize the tear film. Ibuprofen was employed as the model
NSAID, chitosan as the cationic agent, and lecithin as the anionic
surfactant enabling chitosan incorporation. Moreover, lecithin is a
mixture of phospholipids including phosphatidylcholine and
phosphatidylethanolamine, two constituents of the natural tear film
important for its stability. NEs were characterized in terms of droplet
size, polydispersity index, zeta-potential, pH, viscosity, osmolarity,
surface tension, entrapment efficiency, stability, sterilizability and in
vitro release. NEs mucoadhesive properties were tested rheologically
after mixing with mucin dispersion. Biocompatibility was assessed
employing 3D HCE-T cell-based model and ex vivo model using porcine
corneas. The results of our study pointed out the NE formulation with
0.05 % (w/w) chitosan as the lead formulation with physicochemical
properties adequate for ophthalmic application, mucoadhesive character
and excellent biocompatibility.
PB  - Elsevier
T2  - International Journal of Pharmaceutics
T1  - Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment
VL  - 576
SP  - 118979
DO  - 10.1016/j.ijpharm.2019.118979
ER  - 
@article{
author = "Jurišić Dukovski, Bisera and Juretić, Marina and Bračko, Danka and Randjelović, Danijela and Savić, Snežana and Crespo Moral, Mario and Diebold, Yolanda and Filipović-Grčić, Jelena and Pepić, Ivan and Lovrić, Jasmina",
year = "2020",
abstract = "Abstract: Inflammation plays a key role in dry eye disease (DED)
affecting millions of people worldwide. Non-steroidal anti-inflammatory
drugs (NSAIDs) can be used topically to act on the inflammatory component
of DED, but their limited aqueous solubility raises formulation issues.
The aim of this study was development and optimization of functional
cationic nanoemulsions (NEs) for DED treatment, as a formulation approach
to circumvent solubility problems, prolong drug residence at the ocular
surface and stabilize the tear film. Ibuprofen was employed as the model
NSAID, chitosan as the cationic agent, and lecithin as the anionic
surfactant enabling chitosan incorporation. Moreover, lecithin is a
mixture of phospholipids including phosphatidylcholine and
phosphatidylethanolamine, two constituents of the natural tear film
important for its stability. NEs were characterized in terms of droplet
size, polydispersity index, zeta-potential, pH, viscosity, osmolarity,
surface tension, entrapment efficiency, stability, sterilizability and in
vitro release. NEs mucoadhesive properties were tested rheologically
after mixing with mucin dispersion. Biocompatibility was assessed
employing 3D HCE-T cell-based model and ex vivo model using porcine
corneas. The results of our study pointed out the NE formulation with
0.05 % (w/w) chitosan as the lead formulation with physicochemical
properties adequate for ophthalmic application, mucoadhesive character
and excellent biocompatibility.",
publisher = "Elsevier",
journal = "International Journal of Pharmaceutics",
title = "Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment",
volume = "576",
pages = "118979",
doi = "10.1016/j.ijpharm.2019.118979"
}
Jurišić Dukovski, B., Juretić, M., Bračko, D., Randjelović, D., Savić, S., Crespo Moral, M., Diebold, Y., Filipović-Grčić, J., Pepić, I.,& Lovrić, J.. (2020). Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment. in International Journal of Pharmaceutics
Elsevier., 576, 118979.
https://doi.org/10.1016/j.ijpharm.2019.118979
Jurišić Dukovski B, Juretić M, Bračko D, Randjelović D, Savić S, Crespo Moral M, Diebold Y, Filipović-Grčić J, Pepić I, Lovrić J. Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment. in International Journal of Pharmaceutics. 2020;576:118979.
doi:10.1016/j.ijpharm.2019.118979 .
Jurišić Dukovski, Bisera, Juretić, Marina, Bračko, Danka, Randjelović, Danijela, Savić, Snežana, Crespo Moral, Mario, Diebold, Yolanda, Filipović-Grčić, Jelena, Pepić, Ivan, Lovrić, Jasmina, "Functional ibuprofen-loaded cationic nanoemulsion: Development and optimization for dry eye disease treatment" in International Journal of Pharmaceutics, 576 (2020):118979,
https://doi.org/10.1016/j.ijpharm.2019.118979 . .

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