Caspofungin formulations for buccal and sublingual mucosae anti-fungal infections: physicochemical characterization, rheological analysis, release and ex vivo permeability profiles.

Abstract

Aim: Oral candidiasis is often challenging due to limited effectiveness of topical treatments. This study aimed to develop novel caspofungin formulations for administration onto the oral mucosa to enhance drug retention and efficacy.

Method: Five caspofungin (2%, w/v) formulations were developed to assess their permeability, retention and mucoadhesiveness. Ex vivo permeability assays were performed on buccal and sublingual mucosae, and histological analyses conducted to evaluate tissue tolerance.

Results: Formulation composed of chitosan demonstrated the highest retention in both buccal (5183.24 ± 587.32 µg/cm²) and sublingual (1090.72 ± 110.26 µg/cm²) mucosae. Other formulations exhibited significantly lower retention, ranging from 7.53 ± 0.81 to 1852.10 ± 193.24 µg/cm² in buccal mucosa and 1.64 ± 0.14 to 317.74 ± 31.78 µg/cm² in sublingual mucosa. Chitosan-based formulation exhibited the highest mucoadhesive strength, with values of 5179.05 ± 31.99 mN/cm² for buccal and 7026.10 ± 123.41 mN/cm² for sublingual mucosae, and also superior extensibility, which facilitates application in the oral cavity. All formulations showed antifungal activity against Candida spp., and histological analyses revealed minor epithelial alterations.

Conclusion: The developed formulations offer distinct advantages for treating oral candidiasis, with chitosan formulation emerging as the most promising due to its superior retention, mucoadhesion force, and spreadability, making it a potential candidate for further clinical investigation.