Development, skin targeting and antifungal efficacy of topical lipid nanoparticles containing itraconazole
| Autor: | Gabriel Lima Barros de Araujo, Luciana B. Lopes, Vanessa Franco Carvalho Dartora, Julia Sapienza Passos, Luiza Capello de Martino, Kelly Ishida |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Drug
Itraconazole media_common.quotation_subject Pharmaceutical Science 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences Minimum inhibitory concentration 0302 clinical medicine Medicine media_common Transdermal Transepidermal water loss DERMATOPATIAS INFECCIOSAS biology Sporotrichosis business.industry 021001 nanoscience & nanotechnology biology.organism_classification medicine.disease Galleria mellonella Toxicity 0210 nano-technology business medicine.drug |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|