Development, Skin Targeting And Antifungal Efficacy Of Topical Lipid Nanoparticles Containing Itraconazole

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Julia Sapienza PassosLuciana B Lopes

Abstract

Considering the increased incidence of sporotrichosis and other fungal infections in rural and urban areas, and the limitations and adverse effects of oral itraconazole therapy, we studied nanostructured lipid carriers (NLC) as topical delivery systems to increase itraconazole localization in skin lesions and associate efficacy with reduced systemic exposure. Unloaded and itraconazole-loaded NLC showed nanometric size (∼216-340 nm), negative zeta potential (∼ -17 mV), and high entrapment efficiency (∼97%). NLC treatment decreased transepidermal water loss, an index of cutaneous barrier function, in intact skin and in tissues damaged with a linear incision (to mimic lesions) by 23-36%, and reduced drug transdermal delivery by ∼2-fold, demonstrating its ability to localize itraconazole within the skin. The unloaded and itraconazole-loaded NLC were considered safe, as indicated by scores of 0.5 and 0.6 in HET-CAM models, respectively, and lack of toxicity (measured by survival and health index) on the Galleria mellonella larvae. The values obtained for minimum inhibitory concentration and minimum fungicidal concentration on Sporothrix brasiliensis yeasts were 0.25 and 32 μg/mL, respectively. The drug in solution displayed similar ...Continue Reading

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