Development and Evaluation of Oro-Mucosal Drug Delivery System for the Effective Management of Oropharyngeal Candidiasis: An Animal Study

TL;DR

This study developed a new drug delivery system using posaconazole-loaded nanoparticles to effectively treat oral fungal infections in animals.

Contribution

A novel buccal mucoadhesive nanoparticle formulation of posaconazole for sustained release and improved treatment of oropharyngeal candidiasis.

Findings

Chitosan/PLGA nanoparticles prolonged posaconazole release over 60 hours in vitro.

Nanoformulation significantly improved hematological and histopathological changes in candidiasis-infected rats.

Treatment reduced elevated serum CRP and TNF-α levels in infected animals.

Abstract

Background

Oral candidiasis (OC) is a frequently occurring opportunistic fungal infection seen in individuals with weakened immune systems, such as those with AIDS, those with diabetes mellitus, those undergoing chemotherapy for cancer, or those on prolonged antibiotic medication. Traditional formulations for OC, including mouth paints, rinses, troches, lozenges, and oral gels, cannot sustain the salivary levels of active ingredients over an extended duration. Posaconazole is an extended-spectrum triazole antifungal used to treat invasive candidiasis. A sustained release of this agent is essential for maintaining the salivary concentration for a long. Hence, this study was undertaken to develop a safe and effective posaconazole drug formulation for the management of oropharyngeal candidiasis.

Aim

The aim of this study was to develop a safe and effective drug formulation for the management of oropharyngeal candidiasis.

Methods

The study was conducted in two phases namely: experimental phase I (formulation phase) and experimental phase II. Experimental phase I (formulation phase) consisted of drug and excipient procurement, formulation of chitosan-coated poly-lactic-co-glycolic acid (PLGA) nanoparticles, preparation of chitosan-coated PLGA nanoparticles containing posaconazole, and characterization of formulation. Subsequently, the experimental phase II was carried out, which consisted of conducting in vitro and in vivo studies. In vitro studies consisted of assessing the agar gel diffusion method and time-dependent fungicidal activity. In vivo studies were carried out on animal models (rats) after obtaining ethical clearance from the Animal Ethics Committee.

Results

The in vitro release profile of posaconazole from chitosan/PLGA nanoparticles over 60 h showed that the nanoparticles prolonged the posaconazole release. Nanoformulation was found to be quite active against the Candida albicans strain. In candidiasis infection, the results showed an abnormal hematological index. The abnormal hematological indices and the abnormal histopathological changes in candidiasis infection were significantly improved on treatment with nanoformulation. Abnormally increased serum CRP and TNF-α levels were decreased gradually on treatment with the nanoformulation at the end of day 8.

Conclusion

Local treatment of OC with buccal mucoadhesive chitosan-coated nanoparticles of posaconazole was found to be beneficial not only in reducing the overall required dosage and minimizing side effects but also in eliminating the possibility of drug interaction that is encountered during systemic therapy of posaconazole.

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