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Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization

Isoliquiritigenin (ISL), as a natural flavonoid, has been proven to have therapeutic potential for corneal neovascularization (CNV) treatment; however, its therapeutic use is restricted due to its poor aqueous solubility and limited bioavailability. To overcome these limitations, a novel ISL-loaded...

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Autores principales: Zhang, Rui, Yang, Jingjing, Luo, Qing, Shi, Jieran, Xu, Haohang, Zhang, Junjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275503/
https://www.ncbi.nlm.nih.gov/pubmed/35815765
http://dx.doi.org/10.1080/10717544.2022.2096714
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author Zhang, Rui
Yang, Jingjing
Luo, Qing
Shi, Jieran
Xu, Haohang
Zhang, Junjie
author_facet Zhang, Rui
Yang, Jingjing
Luo, Qing
Shi, Jieran
Xu, Haohang
Zhang, Junjie
author_sort Zhang, Rui
collection PubMed
description Isoliquiritigenin (ISL), as a natural flavonoid, has been proven to have therapeutic potential for corneal neovascularization (CNV) treatment; however, its therapeutic use is restricted due to its poor aqueous solubility and limited bioavailability. To overcome these limitations, a novel ISL-loaded nanoemulsion (ISL-NE) was designed for inhibiting CNV in this study. ISL-NE formulation was composed of propylene glycol dicaprylate (PGD), Cremophor® EL (EL35), polyethylene glycol 400 (PEG 400) and adding water with sodium hyaluronate, its particle size was 34.56 ± 0.80 nm with a low polydispersity index of less than 0.05, which suggested a narrow size distribution. The results demonstrated that ISL-NE released higher and permeated more drug than ISL suspension (ISL-Susp) in in vitro drug release and ex vivo corneal permeation study. ISL-NE showed no cytotoxicity in human corneal epithelial cells toxicity study, which was consistent with the result of ocular irritation study in rabbit eyes. ISL-NE had bioavailability 5.76-fold, 7.80-fold and 2.13-fold higher than ISL-Sups in tears, cornea and aqueous humor after a single dose of ISL-NE, respectively. Furthermore, the efficacy of ISL-NE treatment (0.2% ISL) was comparable to that of dexamethasone treatment (0.025%) in the inhibition of CNV in mice model. Enzyme-linked immunosorbent assay (ELISA) showed that the expressions of corneal vascular endothelial growth factor (VEGF-A) and matrix metalloproteinase (MMP-2) were decreased. In conclusion, the ISL-NE demonstrated excellent physicochemical properties, good tolerance, and enhanced ocular bioavailability. It could be a promising, safe, and effective treatment for CNV.
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spelling pubmed-92755032022-07-13 Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization Zhang, Rui Yang, Jingjing Luo, Qing Shi, Jieran Xu, Haohang Zhang, Junjie Drug Deliv Research Article Isoliquiritigenin (ISL), as a natural flavonoid, has been proven to have therapeutic potential for corneal neovascularization (CNV) treatment; however, its therapeutic use is restricted due to its poor aqueous solubility and limited bioavailability. To overcome these limitations, a novel ISL-loaded nanoemulsion (ISL-NE) was designed for inhibiting CNV in this study. ISL-NE formulation was composed of propylene glycol dicaprylate (PGD), Cremophor® EL (EL35), polyethylene glycol 400 (PEG 400) and adding water with sodium hyaluronate, its particle size was 34.56 ± 0.80 nm with a low polydispersity index of less than 0.05, which suggested a narrow size distribution. The results demonstrated that ISL-NE released higher and permeated more drug than ISL suspension (ISL-Susp) in in vitro drug release and ex vivo corneal permeation study. ISL-NE showed no cytotoxicity in human corneal epithelial cells toxicity study, which was consistent with the result of ocular irritation study in rabbit eyes. ISL-NE had bioavailability 5.76-fold, 7.80-fold and 2.13-fold higher than ISL-Sups in tears, cornea and aqueous humor after a single dose of ISL-NE, respectively. Furthermore, the efficacy of ISL-NE treatment (0.2% ISL) was comparable to that of dexamethasone treatment (0.025%) in the inhibition of CNV in mice model. Enzyme-linked immunosorbent assay (ELISA) showed that the expressions of corneal vascular endothelial growth factor (VEGF-A) and matrix metalloproteinase (MMP-2) were decreased. In conclusion, the ISL-NE demonstrated excellent physicochemical properties, good tolerance, and enhanced ocular bioavailability. It could be a promising, safe, and effective treatment for CNV. Taylor & Francis 2022-07-10 /pmc/articles/PMC9275503/ /pubmed/35815765 http://dx.doi.org/10.1080/10717544.2022.2096714 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Rui
Yang, Jingjing
Luo, Qing
Shi, Jieran
Xu, Haohang
Zhang, Junjie
Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization
title Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization
title_full Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization
title_fullStr Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization
title_full_unstemmed Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization
title_short Preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization
title_sort preparation and in vitro and in vivo evaluation of an isoliquiritigenin-loaded ophthalmic nanoemulsion for the treatment of corneal neovascularization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275503/
https://www.ncbi.nlm.nih.gov/pubmed/35815765
http://dx.doi.org/10.1080/10717544.2022.2096714
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