Cargando…
An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva
We previously developed ophthalmic formulations containing tranilast nanopartaicles (ophthalmic TL-NPs formulations), and found them to show high uptake into ocular tissues. In this study, we aimed to design an in situ gel incorporating TL-NPs with 0.5–3% methylcellulose (MC, type SM-4) to ensure lo...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358604/ https://www.ncbi.nlm.nih.gov/pubmed/32733870 http://dx.doi.org/10.3389/fbioe.2020.00764 |
_version_ | 1783558877384540160 |
---|---|
author | Nagai, Noriaki Minami, Misa Deguchi, Saori Otake, Hiroko Sasaki, Hiroshi Yamamoto, Naoki |
author_facet | Nagai, Noriaki Minami, Misa Deguchi, Saori Otake, Hiroko Sasaki, Hiroshi Yamamoto, Naoki |
author_sort | Nagai, Noriaki |
collection | PubMed |
description | We previously developed ophthalmic formulations containing tranilast nanopartaicles (ophthalmic TL-NPs formulations), and found them to show high uptake into ocular tissues. In this study, we aimed to design an in situ gel incorporating TL-NPs with 0.5–3% methylcellulose (MC, type SM-4) to ensure long residence time of the drug at the ocular surface. The ophthalmic TL-NPs formulations were prepared by the bead mill method, which yielded a mean particle size of ~93 nm with or without MC (0.5–3%). Although the dispersibility of TL particles in ophthalmic formulations increased with the MC content, the diffusion behavior of TL particles in the dispersion medium decreased with MC content. In an in vivo study using rats, the TL content in the lacrimal fluid was enhanced with MC content in the ophthalmic TL-NPs formulations, and the optimum amount of MC (0.5–1.5%) enhanced the TL content in the cornea and conjunctiva, and an anti-inflammatory effect of TL in rats instilled with ophthalmic TL-NPs formulations was observed. On the other hand, excessive MC (3%) prevented the corneal uptake of TL-NPs after instillation, and the anti-inflammation effect of TL was lower than that of ophthalmic TL-NPs formulations with optimum MC (0.5–1.5%). In conclusion, we found that gel formulations of TL-NPs with 0.5 and 1.5% MC provided a prolonged pre-corneal and pre-conjunctival contact time of TL, and resulted in higher TL contents in the cornea and conjunctiva following instillation in comparison with TL-NPs with or without 3% MC. This is probably due to the balance between the higher residence time and faster diffusion of TL-NPs on the ocular surface. These findings provide significant information that can be used to design further studies aimed at developing ophthalmic nanomedicines. |
format | Online Article Text |
id | pubmed-7358604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73586042020-07-29 An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva Nagai, Noriaki Minami, Misa Deguchi, Saori Otake, Hiroko Sasaki, Hiroshi Yamamoto, Naoki Front Bioeng Biotechnol Bioengineering and Biotechnology We previously developed ophthalmic formulations containing tranilast nanopartaicles (ophthalmic TL-NPs formulations), and found them to show high uptake into ocular tissues. In this study, we aimed to design an in situ gel incorporating TL-NPs with 0.5–3% methylcellulose (MC, type SM-4) to ensure long residence time of the drug at the ocular surface. The ophthalmic TL-NPs formulations were prepared by the bead mill method, which yielded a mean particle size of ~93 nm with or without MC (0.5–3%). Although the dispersibility of TL particles in ophthalmic formulations increased with the MC content, the diffusion behavior of TL particles in the dispersion medium decreased with MC content. In an in vivo study using rats, the TL content in the lacrimal fluid was enhanced with MC content in the ophthalmic TL-NPs formulations, and the optimum amount of MC (0.5–1.5%) enhanced the TL content in the cornea and conjunctiva, and an anti-inflammatory effect of TL in rats instilled with ophthalmic TL-NPs formulations was observed. On the other hand, excessive MC (3%) prevented the corneal uptake of TL-NPs after instillation, and the anti-inflammation effect of TL was lower than that of ophthalmic TL-NPs formulations with optimum MC (0.5–1.5%). In conclusion, we found that gel formulations of TL-NPs with 0.5 and 1.5% MC provided a prolonged pre-corneal and pre-conjunctival contact time of TL, and resulted in higher TL contents in the cornea and conjunctiva following instillation in comparison with TL-NPs with or without 3% MC. This is probably due to the balance between the higher residence time and faster diffusion of TL-NPs on the ocular surface. These findings provide significant information that can be used to design further studies aimed at developing ophthalmic nanomedicines. Frontiers Media S.A. 2020-07-07 /pmc/articles/PMC7358604/ /pubmed/32733870 http://dx.doi.org/10.3389/fbioe.2020.00764 Text en Copyright © 2020 Nagai, Minami, Deguchi, Otake, Sasaki and Yamamoto. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Nagai, Noriaki Minami, Misa Deguchi, Saori Otake, Hiroko Sasaki, Hiroshi Yamamoto, Naoki An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva |
title | An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva |
title_full | An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva |
title_fullStr | An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva |
title_full_unstemmed | An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva |
title_short | An in situ Gelling System Based on Methylcellulose and Tranilast Solid Nanoparticles Enhances Ocular Residence Time and Drug Absorption Into the Cornea and Conjunctiva |
title_sort | in situ gelling system based on methylcellulose and tranilast solid nanoparticles enhances ocular residence time and drug absorption into the cornea and conjunctiva |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358604/ https://www.ncbi.nlm.nih.gov/pubmed/32733870 http://dx.doi.org/10.3389/fbioe.2020.00764 |
work_keys_str_mv | AT nagainoriaki aninsitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT minamimisa aninsitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT deguchisaori aninsitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT otakehiroko aninsitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT sasakihiroshi aninsitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT yamamotonaoki aninsitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT nagainoriaki insitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT minamimisa insitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT deguchisaori insitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT otakehiroko insitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT sasakihiroshi insitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva AT yamamotonaoki insitugellingsystembasedonmethylcelluloseandtranilastsolidnanoparticlesenhancesocularresidencetimeanddrugabsorptionintothecorneaandconjunctiva |