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Open AccessArticle

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

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Laboratory of Drug Delivery Technology, Department of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, Italy
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Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), 3030-548 Coimbra, Portugal
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CNC—Center for Neurosciences and Cell Biology, University of Coimbra, 3030-548 Coimbra, Portugal
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Laboratory of Microbiology, Faculty of Pharmacy, University of Coimbra, 3030-548 Coimbra, Portugal
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Department of Biology and Environment, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, P-5001-801 Vila Real, Portugal
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Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Trás-os-Montes e Alto Douro (UTAD), P-5001-801 Vila Real, Portugal
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REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3030-548 Coimbra, Portugal
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2019, 11(5), 231; https://doi.org/10.3390/pharmaceutics11050231
Received: 9 April 2019 / Revised: 6 May 2019 / Accepted: 9 May 2019 / Published: 13 May 2019
(This article belongs to the Special Issue Advances in Solid Lipid Micro- and Nanoparticle Technology)
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 (23 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. View Full-Text
Keywords: Rosmarinus officinalis L.; Lavandula x intermedia “Sumian”; Origanum vulgare subsp. hirtum; factorial design; stability; Turbiscan; Lumisizer; DSC; cytotoxicity; MIC Rosmarinus officinalis L.; Lavandula x intermedia “Sumian”; Origanum vulgare subsp. hirtum; factorial design; stability; Turbiscan; Lumisizer; DSC; cytotoxicity; MIC
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MDPI and ACS Style

Carbone, C.; Teixeira, M.C.; Sousa, M.C.; Martins-Gomes, C.; Silva, A.M.; Souto, E.M.B.; Musumeci, T. Clotrimazole-Loaded Mediterranean Essential Oils NLC: A Synergic Treatment of Candida Skin Infections. Pharmaceutics 2019, 11, 231.

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