Oleic Acid Vesicles as a New Approach for Transdermal Delivery of Econazole Nitrate: Development, Characterization, and In-vivo Evaluation in Wistar Rats

Abstract

Background:: Cutaneous candidiasis is a deep-seated skin fungal infection that is most commonly observed in immunocompromised patients. This fungal infection is conventionally treated with various formulations like gels and creams which are having different side effects and the least therapeutic efficacy. Hence, it becomes necessary to develop a novel carrier system for the treatment of this deep-seated skin fungal infection. Econazole nitrate is the most widely used antifungal for the treatment of cutaneous candidiasis and many patents have been granted by various pharmaceutical scientists around the globe related to nanocarrier systems for transdermal delivery of antifungal drugs like econazole nitrate (ECN) therefore, we developed and evaluated econazole nitrate loaded oleic acid vesicles in the present research work for treatment of cutaneous candidiasis through transdermal route. Methods:: Econazole nitrate loaded oleic acid vesicles were prepared by thin-film hydration and characterized for drug entrapment, vesicle size, zeta potential, polydispersity index (PDI), Fourier Transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. Furthermore, the oleic acid vesicular gel was evaluated for ex-vivo skin permeation/retention and in-vitro and in-vivo antifungal activity in Wistar rats. Results:: Econazole nitrate loaded oleic acid vesicles showed high encapsulation of drug (74.76 ± 3.0%), acceptable size (373.4 ± 2.9 nm), and colloidal characteristics (PDI = 0.231 ± 0.078, and zeta potential = -13.27 ± 0.80 mV). The oleic acid vesicular gel showed high skin permeation (Transdermal flux = 61.98 ± 2.45 μg/cm2/h), skin retention (35.90 ± 2.06%), in-vitro, and in-vivo antifungal activity compared to marketed cream (Ecoderm R) of econazole nitrate for a prolonged time (4 days). Conclusion:: Developed econazole nitrate loaded oleic acid vesicles could be used effectively in the treatment of cutaneous candidiasis with minimization of side effects of econazole nitrate with increased therapeutic efficacy.