Hydrogel formulations incorporating drug nanocrystals enhance the therapeutic effect of rebamipide in a hamster model for oral mucositis

Noriaki Nagai, Ryotaro Seiriki, Saori Deguchi, Hiroko Otake, Noriko Hiramatsu, Hiroshi Sasaki, Naoki Yamamoto

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number532
Pages (from-to)1-12
Number of pages12
JournalPharmaceutics
Volume12
Issue number6
DOIs
Publication statusPublished - 06-2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

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