Abstract Introduction Fungal infections are common in tropical regions like India, with Candida albicans being a major causative agent. Ketoconazole, a broad-spectrum antifungal, is commonly used to treat candidiasis but was restricted for oral use by the Food Drug Administration in 2013 due to liver toxicity. However, its topical efficacy is limited by the skin’s barrier, particularly the stratum corneum (SC). Objective Formulation, optimization and evaluation of ketoconazole loaded pegylated bilosomal gel for the treatment of topical fungal infection. Methodology Pegylated bilosomes were developed via ethanol injection and optimized using Central Composite Design with Brij ® C2, Span ® 60, bile salt, and stirring speed as variables. The optimized pegylated bilosomes were characterized by polydispersity index (PDI), vesicle size, zeta potential (ZP), and entrapment efficiency (%EE). Then the optimized pegylated bilosome was incorporated into Carbopol ® 980NF to form a bilosomal gel, which was evaluated for in vitro release, antifungal activity, stability, ex vivo skin permeation, Confocal Laser Scanning Microscopy (CLSM), in vivo pharmacodynamics, and histopathology studies. Results The optimized pegylated bilosomes showed small vesicle size (229.9 nm) with PDI (0.206), ZP (-36.8 mV), & %EE (70.88). Transmission electron microscopy and deformability studies indicated vesicle morphology and elasticity. The 0.3% w/w bilosomal gel achieved 63.60 ± 1.93% in vitro drug release in 8 h and demonstrated enhanced antifungal activity against Candida albicans . Ex vivo studies showed a 2.4-fold increase in skin permeation, and CLSM confirmed deeper epidermal penetration. In vivo, the gel significantly reduced fungal load in infected rats, with histopathology confirming its safety and non-irritancy. Conclusion The optimized pegylated bilosomes offer a promising platform for targeted topical antifungal delivery, ensuring improved drug penetration, and site-specific action. This nanocarrier approach can significantly enhance therapeutic outcomes while reducing systemic exposure, establishing a clinically relevant, and good alternative to conventional antifungal formulations.
Nayak et al. (Thu,) studied this question.