Abstract
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.
Highlights
The worldwide incidence of serious systemic infections has extremely increased, most of these due to fungi of Candida species, causing severe opportunistic infections in immuno-compromised patients, especially those affected by cancer, diabetes and AIDS [1]
We recently found that Rosmarinus officinalis, Lavandula x intermedia “Sumian” and Origanum vulgare subsp. hirtum can be successfully used as matrix components and active ingredients of nanostructured lipid carriers (NLC), exploiting their relevant anti-inflammatory activity, enhancing their biocompatibility and reducing the cytotoxicity of the pure oils [15]
Regarding the tested pure essential oils (EOs) (Lavandula and Rosmarinus), little information is provided in the literature, the Minimum inhibitory concentration (MIC) and minimum lethal concentration (MLC) determined for each strain are in accordance to previous findings by Bona et al [8] within the range of 2–4% (v/v) for both EOs in reference and clinical isolated strains of C. albicans
Summary
The worldwide incidence of serious systemic infections has extremely increased, most of these due to fungi of Candida species, causing severe opportunistic infections in immuno-compromised patients, especially those affected by cancer, diabetes and AIDS [1]. Conventional antifungal drugs often show toxic side effects to human cells [5,6] Based on these considerations, researchers’ efforts in developing novel approaches to improve the effective treatment of fungal infection is growing, with a renewed interest in plants and traditional medicine. Researchers’ efforts in developing novel approaches to improve the effective treatment of fungal infection is growing, with a renewed interest in plants and traditional medicine In this field, increasing attention has been paid to essential oils (EOs) as promising natural compounds for their different activities, such as antibacterial, antifungal, antiviral, antioxidant, anticancer, immune-modulatory, analgesic and anti-inflammatory [7,8]. Other authors reported the possibility to exploit different drug delivery systems for the encapsulation of EOs, such as polymeric poly(varepsilon-caprolactone) (PCL) nanocapsules [20], chitosan nanoparticles [13,21]
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