Development, skin targeting and antifungal efficacy of topical lipid nanoparticles containing itraconazole

Julia Sapienza Passos; Luiza Capello de Martino; Vanessa Franco Carvalho Dartora; Gabriel L B de Araujo; Kelly Ishida; Luciana B Lopes

doi:10.1016/j.ejps.2020.105296

Development, skin targeting and antifungal efficacy of topical lipid nanoparticles containing itraconazole

Eur J Pharm Sci. 2020 Mar 7:149:105296. doi: 10.1016/j.ejps.2020.105296. Online ahead of print.

Authors

Julia Sapienza Passos¹, Luiza Capello de Martino¹, Vanessa Franco Carvalho Dartora², Gabriel L B de Araujo³, Kelly Ishida², Luciana B Lopes⁴

Affiliations

¹ Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil; School of Pharmaceutical Sciences of São Paulo, University of São Paulo, São Paulo, SP, Brazil.
² Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
³ School of Pharmaceutical Sciences of São Paulo, University of São Paulo, São Paulo, SP, Brazil.
⁴ Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address: lublopes@usp.br.

PMID: 32151706
DOI: 10.1016/j.ejps.2020.105296

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 values, indicating that encapsulation does not hinder itraconazole antifungal effect. NLC treatment improved the survival rate and health index of G. mellonella larvae infected with S. brasiliensis yeasts and C. albicans, demonstrating antifungal efficacy. Taken together, itraconazole encapsulation in NLC represents a viable strategy to optimize cutaneous localization without compromising its efficacy against fungal infections.

Keywords: Itraconazole; Nanoparticle; Nanostructured lipid carriers; Skin; Sporotrichosis; Topical.