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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2022
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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. |
format | Online Article Text |
id | pubmed-9275503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
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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