Development and Evaluation of Voriconazole-Loaded Ethosomal Gel for Enhanced Topical Delivery in Cutaneous Candidiasis

Background/Objectives

Cutaneous candidiasis remains a significant clinical challenge, particularly in warm, moist body regions and immunocompromised individuals. This study focuses on the development and evaluation of a topical ethosomal gel of Voriconazole, a BCS Class II antifungal drug with poor aqueous solubility.

Materials and Methods

Ethosomes, characterized by high ethanol content and lipid bilayers, were engineered to bypass the stratum corneum barrier. Seven formulations (F1-F7) were prepared using varying ratios of lecithin, cholesterol, and ethanol. The optimized ethosomes were successfully incorporated into a Carbopol 934P gel base. In vivo skin irritancy tests on Wistar rats were performed to evaluate dermal tolerability.

Results

Batch F7 was identified as the optimized formulation, exhibiting a particle size of 370.8 nm, a zeta potential of -18.6 mV, and a high entrapment efficiency of 72.33%. In vitro diffusion studies demonstrated a sustained drug release of 88.89% over 270 min, significantly outperforming plain gel formulations. The optimized ethosomal gel also showed promising antifungal activity against Candida albicans with zones of inhibition comparable to standard voriconazole, and remained stable during accelerated stability studies, showing only a slight reduction in entrapment efficiency after 3 months. Furthermore, in vivo skin irritancy tests on Wistar rats classified the formulation as non-irritant (PII: 0.34).

Conclusion

This study presents a voriconazole-loaded ethosomal gel optimized for topical delivery and evaluated for sustained release, antifungal activity, skin tolerability, and stability, thereby offering a potential nanovesicular alternative for cutaneous candidiasis management. These ethosomal gels are a viable, patient-compliant alternative for enhancing the local delivery of poorly soluble antifungal agents.