Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of Leishmania braziliensis Infection

• Published in: International journal of nanomedicine Vol. 15; pp. 8659 - 8672
• Main Authors: Rebouças-Silva, Jéssica, Tadini, Maraine Catarina, Devequi-Nunes, Danielle, Mansur, Ana Luíza, S Silveira-Mattos, Paulo, I de Oliveira, Camila, R Formiga, Fábio, Berretta, Andresa A, Marquele-Oliveira, Franciane, Borges, Valéria M
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2020; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Amphotericin B; Amphotericin B - administration & dosage; Amphotericin B - pharmacokinetics; Amphotericin B - pharmacology; Analysis; Animals; Antifungal agents; Antiparasitic agents; Atomic force microscopy; Cytotoxicity; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - therapeutic use; Drug Carriers - administration & dosage; Drug Carriers - pharmacokinetics; Drug Carriers - therapeutic use; drug delivery; Drug delivery systems; Drug Delivery Systems - methods; Drugs; Female; Health aspects; Hydrogen-Ion Concentration; Infection; Leishmania braziliensis - drug effects; Leishmania braziliensis - pathogenicity; Leishmaniasis; Leishmaniasis, Cutaneous - drug therapy; Lipids; Lipids - chemistry; Macrophages - drug effects; Macrophages - parasitology; Male; Mice, Inbred BALB C; Microemulsions; Nanoparticles; Nanostructures - administration & dosage; Nanostructures - chemistry; neglected disease; Nitric oxide; Original Research; Parasitic diseases; Penicillin; Surfactants; Tropical diseases; Vehicles; Brazil; Germany; St Louis Missouri; United States > US; China; nanoparticles; drug delivery; leishmaniasis; neglected disease
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S262642

Leishmaniasis is a neglected disease, and the current therapeutic arsenal for its treatment is seriously limited by high cost and toxicity. Nanostructured lipid carriers (NLCs) represent a promising approach due to high drug loading capacity, controlled drug release profiles and superior stability. Here, we explore the efficacy of a unique pH-sensitive amphotericin B-loaded NLC (AmB-NLC) in infection in vitro and in vivo. AmB-NLC was assessed by dynamic light scattering and atomic force microscopy assays. The carrier showed a spherical shape with a nanometric size of 242.0 ± 18.3 nm. Zeta potential was suggestive of high carrier stability (-42.5 ± 1.5 mV), and the NLC showed ~99% drug encapsulation efficiency (EE%). In biological assays, AmB-NLC presented a similar IC as free AmB and conventional AmB deoxycholate (AmB-D) (11.7 ± 1.73; 5.3 ± 0.55 and 13 ± 0.57 ng/mL, respectively), while also presenting higher selectivity index and lower toxicity to host cells, with no observed production of nitric oxide or TNF-α by in vitro assay. Confocal microscopy revealed the rapid uptake of AmB-NLC by infected macrophages after 1h, which, in association with more rapid disruption of AmB-NLC at acidic pH levels, may directly affect intracellular parasites. Leishmanicidal effects were evaluated in vivo in BALB/c mice infected in the ear dermis with and treated with a pentavalent antimonial (Sb ), liposomal AmB (AmB-L) or AmB-NLC. After 6 weeks of infection, AmB-NLC treatment resulted in smaller ear lesion size in all treated mice, indicating the efficacy of the novel formulation. Here, we preliminarily demonstrate the effectiveness of an innovative and cost-effective AmB-NLC formulation in promoting the killing of intracellular . This novel carrier system could be a promising alternative for the future treatment of cutaneous leishmaniasis.