Innovative green niosomal piperlongumine as a novel topical treatment for dermatophytosis in guinea pigs model

Abstract Dermatophytosis is a common superficial fungal infection that affects many people worldwide. Although various species of dermatophytes respond to common antifungal drugs, the recently identified Trichophyton indotineae isolates have exhibited significant terbinafine resistance due to mutations in the Squalene Epoxidase (SQLE) gene. Piperlongumine (PL), a natural alkaloid that stimulates ROS production and inhibits some crucial enzymes, has a good capacity to treat these fungal infections. As part of nanotechnology, niosomes can increase the success of the drug by targeting the affected areas. This study investigates the effectiveness of PL niosomal gel 1% in an infected animal model with T. indotineae, providing important insights for infection treatment. Thirty guinea pigs empirically infected with T. indotineae were divided into five groups (e.g., untreated control, treated groups with terbinafine 1%, niosome, PL gel 1%, and PL niosomal gel 1%) and subsequently scored both clinically and mycologically until the 38th day of inoculation. On the 38th day of the study, histological evaluation was performed. In contrast to the terbinafine group, which demonstrated no efficacy (P < 0.05), the 1% PL niosomal gel significantly decreased mycological and clinical lesion scores, leading to complete mycological cure (negative fungal cultures) by day 28. Moreover, histopathological analysis confirmed that this compound reduced epidermal thickness, fungal burden, and inflammation. However, it should be noted that the difference in recovery rate of pigs with PL gel 1% and PL niosomal gel 1% was not statistically significant (p = 0.6). Treatment of T. indotineae dermatophytosis using PL niosomal gel is a safer and more effective alternative to conventional topical and oral antifungal therapies. However, further studies are warranted to correlate these findings with clinical outcomes.