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In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics
Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therap...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238180/ https://www.ncbi.nlm.nih.gov/pubmed/32326492 http://dx.doi.org/10.3390/pharmaceutics12040360 |
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author | Destruel, Pierre-Louis Zeng, Ni Brignole-Baudouin, Françoise Douat, Sophie Seguin, Johanne Olivier, Elodie Dutot, Melody Rat, Patrice Dufaÿ, Sophie Dufaÿ-Wojcicki, Amélie Maury, Marc Mignet, Nathalie Boudy, Vincent |
author_facet | Destruel, Pierre-Louis Zeng, Ni Brignole-Baudouin, Françoise Douat, Sophie Seguin, Johanne Olivier, Elodie Dutot, Melody Rat, Patrice Dufaÿ, Sophie Dufaÿ-Wojcicki, Amélie Maury, Marc Mignet, Nathalie Boudy, Vincent |
author_sort | Destruel, Pierre-Louis |
collection | PubMed |
description | Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therapeutic strategy has reached the market. The present work focuses on the formulation and evaluation of a mucoadhesive ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose (HEC) for the delivery of phenylephrine and tropicamide. First, in vitro drug release was studied to assess appropriate sustained drug delivery on the ocular surface region. Drug release mechanisms were explored and explained using mathematical modeling. Then, in situ gelling delivery systems were visualized using scanning electron microscopy illustrating the drug release phenomena involved. Afterward, cytotoxicity of the developed formulations was studied and compared with those of commercially available eye drops. Human epithelial corneal cells were used. Finally, mydriasis intensity and kinetic was investigated in vivo. Mydriasis pharmacodynamics was studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. In situ gelling delivery systems mydriasis profiles exhibited a significant increase of intensity and duration compared with those of conventional eye drops. Efficient mydriasis was achieved following the administration of a single drop of in situ gel reducing the required amount of administered active ingredients by four- to eight-fold compared with classic eye drop regimen. |
format | Online Article Text |
id | pubmed-7238180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72381802020-05-28 In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics Destruel, Pierre-Louis Zeng, Ni Brignole-Baudouin, Françoise Douat, Sophie Seguin, Johanne Olivier, Elodie Dutot, Melody Rat, Patrice Dufaÿ, Sophie Dufaÿ-Wojcicki, Amélie Maury, Marc Mignet, Nathalie Boudy, Vincent Pharmaceutics Article Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therapeutic strategy has reached the market. The present work focuses on the formulation and evaluation of a mucoadhesive ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose (HEC) for the delivery of phenylephrine and tropicamide. First, in vitro drug release was studied to assess appropriate sustained drug delivery on the ocular surface region. Drug release mechanisms were explored and explained using mathematical modeling. Then, in situ gelling delivery systems were visualized using scanning electron microscopy illustrating the drug release phenomena involved. Afterward, cytotoxicity of the developed formulations was studied and compared with those of commercially available eye drops. Human epithelial corneal cells were used. Finally, mydriasis intensity and kinetic was investigated in vivo. Mydriasis pharmacodynamics was studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. In situ gelling delivery systems mydriasis profiles exhibited a significant increase of intensity and duration compared with those of conventional eye drops. Efficient mydriasis was achieved following the administration of a single drop of in situ gel reducing the required amount of administered active ingredients by four- to eight-fold compared with classic eye drop regimen. MDPI 2020-04-15 /pmc/articles/PMC7238180/ /pubmed/32326492 http://dx.doi.org/10.3390/pharmaceutics12040360 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Destruel, Pierre-Louis Zeng, Ni Brignole-Baudouin, Françoise Douat, Sophie Seguin, Johanne Olivier, Elodie Dutot, Melody Rat, Patrice Dufaÿ, Sophie Dufaÿ-Wojcicki, Amélie Maury, Marc Mignet, Nathalie Boudy, Vincent In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics |
title | In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics |
title_full | In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics |
title_fullStr | In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics |
title_full_unstemmed | In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics |
title_short | In Situ Gelling Ophthalmic Drug Delivery System for the Optimization of Diagnostic and Preoperative Mydriasis: In Vitro Drug Release, Cytotoxicity and Mydriasis Pharmacodynamics |
title_sort | in situ gelling ophthalmic drug delivery system for the optimization of diagnostic and preoperative mydriasis: in vitro drug release, cytotoxicity and mydriasis pharmacodynamics |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238180/ https://www.ncbi.nlm.nih.gov/pubmed/32326492 http://dx.doi.org/10.3390/pharmaceutics12040360 |
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