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Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis

A mouthwash formulation of rebamipide (REB) is commonly used to treat oral mucositis; however, this formulation does not provide sufficient treatment or prevention in cases of serious oral mucositis. To improve treatment, we attempted to design a hydrogel incorporating REB nanocrystals (R-NPs gel)....

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Detalles Bibliográficos
Autores principales: Nagai, Noriaki, Seiriki, Ryotaro, Deguchi, Saori, Otake, Hiroko, Hiramatsu, Noriko, Sasaki, Hiroshi, Yamamoto, Naoki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356607/
https://www.ncbi.nlm.nih.gov/pubmed/32527029
http://dx.doi.org/10.3390/pharmaceutics12060532
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author Nagai, Noriaki
Seiriki, Ryotaro
Deguchi, Saori
Otake, Hiroko
Hiramatsu, Noriko
Sasaki, Hiroshi
Yamamoto, Naoki
author_facet Nagai, Noriaki
Seiriki, Ryotaro
Deguchi, Saori
Otake, Hiroko
Hiramatsu, Noriko
Sasaki, Hiroshi
Yamamoto, Naoki
author_sort Nagai, Noriaki
collection PubMed
description A mouthwash formulation of rebamipide (REB) is commonly used to treat oral mucositis; however, this formulation does not provide sufficient treatment or prevention in cases of serious oral mucositis. To improve treatment, we attempted to design a hydrogel incorporating REB nanocrystals (R-NPs gel). The R-NPs gel was prepared by a bead mill method using carbopol hydrogel, methylcellulose and 2-hydroxypropyl-β-cyclodextrin, and another hydrogel incorporating REB microcrystals (R-MPs gel) was prepared following the same protocol but without the bead mill treatment. The REB particle size in the R-MPs gel was 0.15–25 μm, and while the REB particle size was 50–180 nm in the R-NPs gel. Next, we investigated the therapeutic effect of REB nanocrystals on oral mucositis using a hamster model. Almost all of the REB was released as drug nanocrystals from the R-NPs gel, and the REB content in the cheek pouch of hamsters treated with R-NPs gel was significantly higher than that of hamsters treated with R-MPs gel. Further, treatment with REB hydrogels enhanced the healing of oral wounds in the hamsters. REB accumulation in the cheek pouch of hamsters treated with the R-NPs gel was prevented by an inhibitor of clathrin-dependent endocytosis (CME) (40 μM dynasore). In conclusion, we designed an R-NPs gel and found that REB nanocrystals are taken up by tissues through CME, where they provide a persistent effect resulting in an enhancement of oral wound healing.
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spelling pubmed-73566072020-07-22 Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis Nagai, Noriaki Seiriki, Ryotaro Deguchi, Saori Otake, Hiroko Hiramatsu, Noriko Sasaki, Hiroshi Yamamoto, Naoki Pharmaceutics Article A mouthwash formulation of rebamipide (REB) is commonly used to treat oral mucositis; however, this formulation does not provide sufficient treatment or prevention in cases of serious oral mucositis. To improve treatment, we attempted to design a hydrogel incorporating REB nanocrystals (R-NPs gel). The R-NPs gel was prepared by a bead mill method using carbopol hydrogel, methylcellulose and 2-hydroxypropyl-β-cyclodextrin, and another hydrogel incorporating REB microcrystals (R-MPs gel) was prepared following the same protocol but without the bead mill treatment. The REB particle size in the R-MPs gel was 0.15–25 μm, and while the REB particle size was 50–180 nm in the R-NPs gel. Next, we investigated the therapeutic effect of REB nanocrystals on oral mucositis using a hamster model. Almost all of the REB was released as drug nanocrystals from the R-NPs gel, and the REB content in the cheek pouch of hamsters treated with R-NPs gel was significantly higher than that of hamsters treated with R-MPs gel. Further, treatment with REB hydrogels enhanced the healing of oral wounds in the hamsters. REB accumulation in the cheek pouch of hamsters treated with the R-NPs gel was prevented by an inhibitor of clathrin-dependent endocytosis (CME) (40 μM dynasore). In conclusion, we designed an R-NPs gel and found that REB nanocrystals are taken up by tissues through CME, where they provide a persistent effect resulting in an enhancement of oral wound healing. MDPI 2020-06-09 /pmc/articles/PMC7356607/ /pubmed/32527029 http://dx.doi.org/10.3390/pharmaceutics12060532 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
Seiriki, Ryotaro
Deguchi, Saori
Otake, Hiroko
Hiramatsu, Noriko
Sasaki, Hiroshi
Yamamoto, Naoki
Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis
title Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis
title_full Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis
title_fullStr Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis
title_full_unstemmed Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis
title_short Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis
title_sort hydrogel formulations incorporating drug nanocrystals enhance the therapeutic effect of rebamipide in a hamster model for oral mucositis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356607/
https://www.ncbi.nlm.nih.gov/pubmed/32527029
http://dx.doi.org/10.3390/pharmaceutics12060532
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