Dermal Targeting Delivery of Terbinafine Hydrochloride Using Novel Multi-Ethosomes: A New Approach to Fungal Infection Treatment

This research aimed to develop and evaluate a novel multi-ethosome (ME) system for the dermal delivery of terbinafine hydrochloride (TH) as a new approach to fungal infection treatment. TH-loaded MEs were successfully prepared using cinnamaldehyde as a penetration enhancer. Mean diameter of ME was found as ~100 nm with monodispersed size distribution. Drug entrapment efficiency reached up to 86% ± 1.4%. MEs exhibited excellent colloid stability and no drug leakage after 2 months of storage. In contrast to a commercial Lamisil® cream, ME significantly improved the targeting efficiency by increasing the fluidity of stratum corneum layer, revealed by attenuated total reflection Fourier transformed infrared spectroscopy (ATR-FTIR). The dermal targeting effect was visualized using confocal microscopy. Moreover, skin irritation and allergy tests showed that ME was not irritating to the skin. The improved antifungal activity of ME was proved in vitro on Candida albicans strains by minimal inhibitory concentration (MIC) assay. This study paves the way towards design of MEs for dermal fungal infection treatment.