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In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals
We previously designed an ophthalmic dispersion containing indomethacin nanocrystals (IMC-NCs), showing that multiple energy-dependent endocytoses led to the enhanced absorption of drugs from ocular dosage forms. In this study, we attempted to prepare Pluronic F-127 (PLF-127)-based in situ gel (ISG)...
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/PMC7582645/ https://www.ncbi.nlm.nih.gov/pubmed/32992931 http://dx.doi.org/10.3390/ijms21197083 |
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author | Nagai, Noriaki Isaka, Takumi Deguchi, Saori Minami, Misa Yamaguchi, Mizuki Otake, Hiroko Okamoto, Norio Nakazawa, Yosuke |
author_facet | Nagai, Noriaki Isaka, Takumi Deguchi, Saori Minami, Misa Yamaguchi, Mizuki Otake, Hiroko Okamoto, Norio Nakazawa, Yosuke |
author_sort | Nagai, Noriaki |
collection | PubMed |
description | We previously designed an ophthalmic dispersion containing indomethacin nanocrystals (IMC-NCs), showing that multiple energy-dependent endocytoses led to the enhanced absorption of drugs from ocular dosage forms. In this study, we attempted to prepare Pluronic F-127 (PLF-127)-based in situ gel (ISG) incorporating IMC-NCs, and we investigated whether the instillation of the newly developed ISG incorporating IMC-NCs prolonged the precorneal resident time of the drug and improved ocular bioavailability. The IMC-NC-incorporating ISG was prepared using the bead-mill method and PLF-127, which yielded a mean particle size of 50–150 nm. The viscosity of the IMC-NC-incorporating ISG was higher at 37 °C than at 10 °C, and the diffusion and release of IMC-NCs in the IMC-NC-incorporating ISG were decreased by PLF-127 at 37 °C. In experiments using rabbits, the retention time of IMC levels in the lacrimal fluid was enhanced with PLF-127 in the IMC-NC-incorporating ISG, whereby the IMC-NC-incorporating ISG with 5% and 10% PLF-127 increased the transcorneal penetration of the IMCs. In contrast to the results with optimal PLF-127 (5% and 10%), excessive PLF-127 (15%) decreased the uptake of IMC-NCs after instillation. In conclusion, we found that IMC-NC-incorporating ISG with an optimal amount of PLF-127 (5–10%) resulted in higher IMC corneal permeation after instillation than that with excessive PLF-127, probably because of the balance between higher residence time and faster diffusion of IMC-NCs on the ocular surface. These findings provide significant information for developing ophthalmic nanomedicines. |
format | Online Article Text |
id | pubmed-7582645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75826452020-10-28 In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals Nagai, Noriaki Isaka, Takumi Deguchi, Saori Minami, Misa Yamaguchi, Mizuki Otake, Hiroko Okamoto, Norio Nakazawa, Yosuke Int J Mol Sci Article We previously designed an ophthalmic dispersion containing indomethacin nanocrystals (IMC-NCs), showing that multiple energy-dependent endocytoses led to the enhanced absorption of drugs from ocular dosage forms. In this study, we attempted to prepare Pluronic F-127 (PLF-127)-based in situ gel (ISG) incorporating IMC-NCs, and we investigated whether the instillation of the newly developed ISG incorporating IMC-NCs prolonged the precorneal resident time of the drug and improved ocular bioavailability. The IMC-NC-incorporating ISG was prepared using the bead-mill method and PLF-127, which yielded a mean particle size of 50–150 nm. The viscosity of the IMC-NC-incorporating ISG was higher at 37 °C than at 10 °C, and the diffusion and release of IMC-NCs in the IMC-NC-incorporating ISG were decreased by PLF-127 at 37 °C. In experiments using rabbits, the retention time of IMC levels in the lacrimal fluid was enhanced with PLF-127 in the IMC-NC-incorporating ISG, whereby the IMC-NC-incorporating ISG with 5% and 10% PLF-127 increased the transcorneal penetration of the IMCs. In contrast to the results with optimal PLF-127 (5% and 10%), excessive PLF-127 (15%) decreased the uptake of IMC-NCs after instillation. In conclusion, we found that IMC-NC-incorporating ISG with an optimal amount of PLF-127 (5–10%) resulted in higher IMC corneal permeation after instillation than that with excessive PLF-127, probably because of the balance between higher residence time and faster diffusion of IMC-NCs on the ocular surface. These findings provide significant information for developing ophthalmic nanomedicines. MDPI 2020-09-25 /pmc/articles/PMC7582645/ /pubmed/32992931 http://dx.doi.org/10.3390/ijms21197083 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 Nagai, Noriaki Isaka, Takumi Deguchi, Saori Minami, Misa Yamaguchi, Mizuki Otake, Hiroko Okamoto, Norio Nakazawa, Yosuke In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals |
title | In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals |
title_full | In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals |
title_fullStr | In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals |
title_full_unstemmed | In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals |
title_short | In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals |
title_sort | in situ gelling systems using pluronic f127 enhance corneal permeability of indomethacin nanocrystals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582645/ https://www.ncbi.nlm.nih.gov/pubmed/32992931 http://dx.doi.org/10.3390/ijms21197083 |
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