13 May 2019
The increasing development of resistance of Candida 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 3 full factorial design) Mediterranean essential oil ( Rosmarinus officinalis, Lavandula x intermedia “Sumian”, Origanum vulgare subsp. hirtum) lipid nanoparticles for clotrimazole delivery, exploring the potential synergistic effects against Candida 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 Lavandula and Rosmarinus 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 Candida albicans, Candida krusei and Candida parapsilosis, showed an increase of the antifungal activity of clotrimazole-loaded nanoparticles prepared with Lavandula or Rosmarinus, thus confirming nanostructured lipid carriers (NLC) containing Mediterranean essential oils represent a promising strategy to improve drug effectiveness against topical candidiasis.