COMPREHENSIVE EVALUATION OF THE THERAPEUTIC EFFICACY, SAFETY, AND HISTOPATHOLOGICAL IMPACT OF OPTIMIZED DRUG-LOADED MICROSPONGE GEL FOR TREATING CUTANEOUS INFECTIONS IN IMMUNOSUPPRESSED RATS

Abstract

The purpose of this study was to assess the efficiency of an optimized microsponge gel formulation of posaconazole and neomycin gel (PNMG-8) against Candida albicans and Escherichia coli infections in immunosuppressed rats and to compare its efficacy vis-à-vis conventional gels using clinical and histopathological assessments and evaluation of irritancy. The study focused mainly on assessing in-vivo antifungal and antibacterial activity of the optimized microsponge gel formulation for the treatment of cutaneous infections, in particular by Candida albicans and Escherichia coli, using immunosuppressed Wistar rats as the model, with induction of infection by intradermal injection of fungal and bacterial suspensions. Treatment of the rats was by topical application of the PNMG-8 gel, the conventional PCZ/NMN gel, and vehicle control. The therapeutic assessment was based on clinical evaluations, histopathological assessments, and a primary irritancy index (PII) scoring system. The results indicated that PNMG-8 gel significantly reduced fungal-induced skin morphology and histopathology alterations in comparison with the conventional gel and vehicle controls. Clinical signs, including inflammatory changes, oedema, scaling, and rashes, were greatly reduced in rats treated with PNMG-8. The histopathological analysis revealed that the PNMG-8-treated group displayed less fungal growth, inflammatory infiltration, and epidermal changes. Interestingly, PNMG-8 had a lower primary irritating index (PII), indicating better compatibility with the skin. Controlled and sustained release of both active antifungal and antibacterial agents from the microsponge delivery system accounts for the increased therapeutic efficacy of PNMG-8 gel. In conclusion, this study identified the PNMG-8 gel as a potentially promising formulation for safe and effective treatment of cutaneous fungal and bacterial infections, but the observation warrants validation in the clinics.