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Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles

We prepared magnesium hydroxide (MH) nanoparticles, and investigated their effect when combined with dissolved carteolol on the bioavailability and intraocular pressure (IOP)-reducing effect of carteolol. The carteolol was solved in saline containing additives (0.5% methylcellulose, 0.001% benzalkon...

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Autores principales: Nagai, Noriaki, Yamaoka, Sakie, Fukuoka, Yuya, Ishii, Miyu, Otake, Hiroko, Kanai, Kazutaka, Okamoto, Norio, Shimomura, Yoshikazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796228/
https://www.ncbi.nlm.nih.gov/pubmed/29342127
http://dx.doi.org/10.3390/ijms19010282
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author Nagai, Noriaki
Yamaoka, Sakie
Fukuoka, Yuya
Ishii, Miyu
Otake, Hiroko
Kanai, Kazutaka
Okamoto, Norio
Shimomura, Yoshikazu
author_facet Nagai, Noriaki
Yamaoka, Sakie
Fukuoka, Yuya
Ishii, Miyu
Otake, Hiroko
Kanai, Kazutaka
Okamoto, Norio
Shimomura, Yoshikazu
author_sort Nagai, Noriaki
collection PubMed
description We prepared magnesium hydroxide (MH) nanoparticles, and investigated their effect when combined with dissolved carteolol on the bioavailability and intraocular pressure (IOP)-reducing effect of carteolol. The carteolol was solved in saline containing additives (0.5% methylcellulose, 0.001% benzalkonium chloride, 0.5% mannitol; CRT-solution). MH nanoparticles were prepared by a bead mill method with additives. Then carteolol/MH microparticle and carteolol/MH nanoparticle fixed combinations (mCMFC and nCMFC) were prepared by mixing the CRT-solution and MH particles. The transcorneal penetration and IOP-reducing effect of carteolol was evaluated in rabbits. The mean particle size of mCMFC was 7.2 μm, and the particle size was reduced to 73.5–113.5 nm by the bead mill treatment. The MH particles in nCMFC remained in the nano size range for 8 days after preparation, and the amounts of lacrimal fluid and corneal damage were unchanged by repetitive instillation of nCMFC (twice a day for 4 weeks). The transcorneal penetration of carteolol was enhanced by the combination with MH nanoparticles, and the IOP-reducing effect of nCMFC was significantly higher than that of CRT-solution or mCMFC. In conclusion, we designed nCMFC, and showed that the high levels of dissolved carteolol can be delivered into the aqueous humor by the instillation of nCMFC. Combination with MH nanoparticles may achieve an enhancement of corneal penetration for water-soluble drugs. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs.
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spelling pubmed-57962282018-02-09 Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles Nagai, Noriaki Yamaoka, Sakie Fukuoka, Yuya Ishii, Miyu Otake, Hiroko Kanai, Kazutaka Okamoto, Norio Shimomura, Yoshikazu Int J Mol Sci Article We prepared magnesium hydroxide (MH) nanoparticles, and investigated their effect when combined with dissolved carteolol on the bioavailability and intraocular pressure (IOP)-reducing effect of carteolol. The carteolol was solved in saline containing additives (0.5% methylcellulose, 0.001% benzalkonium chloride, 0.5% mannitol; CRT-solution). MH nanoparticles were prepared by a bead mill method with additives. Then carteolol/MH microparticle and carteolol/MH nanoparticle fixed combinations (mCMFC and nCMFC) were prepared by mixing the CRT-solution and MH particles. The transcorneal penetration and IOP-reducing effect of carteolol was evaluated in rabbits. The mean particle size of mCMFC was 7.2 μm, and the particle size was reduced to 73.5–113.5 nm by the bead mill treatment. The MH particles in nCMFC remained in the nano size range for 8 days after preparation, and the amounts of lacrimal fluid and corneal damage were unchanged by repetitive instillation of nCMFC (twice a day for 4 weeks). The transcorneal penetration of carteolol was enhanced by the combination with MH nanoparticles, and the IOP-reducing effect of nCMFC was significantly higher than that of CRT-solution or mCMFC. In conclusion, we designed nCMFC, and showed that the high levels of dissolved carteolol can be delivered into the aqueous humor by the instillation of nCMFC. Combination with MH nanoparticles may achieve an enhancement of corneal penetration for water-soluble drugs. These findings provide significant information that can be used to design further studies aimed at developing anti-glaucoma eye drugs. MDPI 2018-01-17 /pmc/articles/PMC5796228/ /pubmed/29342127 http://dx.doi.org/10.3390/ijms19010282 Text en © 2018 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
Yamaoka, Sakie
Fukuoka, Yuya
Ishii, Miyu
Otake, Hiroko
Kanai, Kazutaka
Okamoto, Norio
Shimomura, Yoshikazu
Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles
title Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles
title_full Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles
title_fullStr Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles
title_full_unstemmed Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles
title_short Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination with Magnesium Hydroxide Nanoparticles
title_sort enhancement in corneal permeability of dissolved carteolol by its combination with magnesium hydroxide nanoparticles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796228/
https://www.ncbi.nlm.nih.gov/pubmed/29342127
http://dx.doi.org/10.3390/ijms19010282
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