Clotrimazole-Loaded Mediterranean Essential Oils NLC: A Synergic Treatment of Skin Infections.

The increasing development of resistance of species to traditional drugs represents a great challenge to the medical field for the treatment of skin infections. Essential oils were recently proposed to increase drug effectiveness. Herein, we developed and optimized (2 full factorial design) Mediterranean essential oil (, x "Sumian", subsp. ) lipid nanoparticles for clotrimazole delivery, exploring the potential synergistic effects against spp. Small sized nanoparticles (<100 nm) with a very broad size distribution (PDI < 0.15) and long-term stability were successfully prepared. Results of the in vitro biosafety on HaCaT (normal cell line) and A431 (tumoral cell line), allowed us to select and as anti-proliferative agents with the potential to be used as co-adjuvants in the treatment of non-tumoral proliferative dermal diseases. Results of calorimetric studies on biomembrane models, confirmed the potential antimicrobial activity of the selected oils due to their interaction with membrane permeabilization. Nanoparticles provided a prolonged in vitro release of clotrimazole. In vitro studies against , and , showed an increase of the antifungal activity of clotrimazole-loaded nanoparticles prepared with or , thus confirming nanostructured lipid carriers (NLC) containing Mediterranean essential oils represent a promising strategy to improve drug effectiveness against topical candidiasis.