Formulation Development of Mucoadhesive Microparticle-Laden Gels for Oral Mucositis: An In Vitro and In Vivo Study.

Yuri Ikeuchi-Takahashi,Nobuyoshi Yoshimura,Chizuko Ishihara,Tohru Aomori,Hiraku Onishi,Ayaka Kobayashi,Hiroomi Sakurai

doi:10.3390/pharmaceutics12070603

Yuri Ikeuchi-Takahashi, Nobuyoshi Yoshimura + Show 5 more

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https://doi.org/10.3390/pharmaceutics12070603

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Abstract

In order to relieve pain due to oral mucositis, we attempted to develop mucoadhesive microparticles containing indomethacin (IM) and gel preparations with IM microparticles that can be applied to the oral cavity. The mucoadhesive microparticles were prepared with a simple composition consisting of IM and polyvinyl alcohol (PVA). Two kinds of PVA with different block properties were used, and microparticles were prepared by heating-filtration and mixing-drying. From the X-ray powder diffraction patterns, differential scanning calorimetry thermograms, and morphological features of the IM microparticles, IM should exist as polymorphic forms in the microparticles. Rapid drug release properties were observed in the IM microparticles. Increased drug retention was observed in IM microparticles containing PVA, and the IM-NK(50) gel, using a common block character PVA and heating-filtration, showed good long-term drug retention properties. In vivo experiments showing significantly higher drug concentrations in the oral mucosa were observed with IM microparticles prepared by heating-filtration, and the IM-NK(50) gel maintained significantly higher drug concentrations in the oral mucosa. From these results, the IM-NK(50) gel may be useful as a preparation for relieving oral mucositis pain.

Highlights

Oral mucositis is one of the most common complications during chemotherapy and some local radiotherapies that can give significant effect on continuation of the therapy
In IM microparticles prepared using the heating-filtration method, IM-NK(50) and IM-KP(50) showed higher PVA content ratio (Pcont) values compared with IM-NK(100) and IM-KP(100)
Because there are no satisfactory preparations to relieve pain due to oral mucositis associated with chemotherapy and/or local radiotherapy, we attempted to develop mucoadhesive microparticle-laden gels that can be applied to the oral cavity

Summary

Introduction

Oral mucositis is one of the most common complications during chemotherapy and some local radiotherapies that can give significant effect on continuation of the therapy. Oral mucositis results in erythema and ulceration of the non-keratinized mucosa, causing suffering pain, decrease in nutritional intake, and bloodstream infections [1,2,3]. Cells in the oral mucosa will be exposed to metabolic damage as a result of their uptake of anticancer agents, ends up in blocking healthy oral mucosal cell turnover. The secondary cause is the adhesion of high levels of oral bacteria to the ulcerated surface, causing local infection on the mucosal surface. In combination with metabolic damage and susceptibility to infection caused by anticancer agents, mucositis can become intractable [6]. No studies of cancer related mucositis with a high evidence level have been published, an effective, reliable method of treatment has yet to be established [7,8]

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