A poly-δ-decalactone (PDL) based nanoemulgel for topical delivery of ketoconazole and eugenol against Candida albicans

Abstract

This study aimed to investigate the potential of poly-δ-decalactone (PDL) and a block copolymer (methoxy-poly(ethylene glycol)-b-poly-δ-decalactone (mPEG-b-PDL)) in the topical delivery of ketoconazole (KTZ) and eugenol (EUG) against Candida albicans. The nanoemulsion (NE) was studied for its significant factors and was optimized using the design of experiments (DOE) methodologies. A simple robust nanoprecipitation method was employed to successfully produce a nanoemulsion (KTZ–EUG–NE). The spherical globules exhibited rough surfaces, explaining the adsorption of mPEG-b-PDL onto PDL. The sustained drug release effects were governed by the amorphous nature of PDL. KTZ–EUG–NE was further used to develop a 1% w/v Carbopol-940-based nanoemulgel (KTZ–EUG–NE gel). The optimal rheological and spreadability properties of the developed nanoemulgel explain the ease of topical applications. Ex vivo permeation and retention studies confirmed the accumulation of KTZ–EUG–NE at different layers of the skin when applied topically. The cytotoxicity of the developed NE in human keratinocyte (HaCaT) cells demonstrated the utility of this newly explored nanocarrier in reducing the cell toxicity of KTZ. The higher antifungal activities of KTZ–EUG–NE at 19.23-fold lower concentrations for planktonic growth and 4-fold lower concentrations for biofilm formation than coarse drugs explain the effectiveness of the developed NE.