Novel and safe single-dose treatment of cutaneous leishmaniasis with implantable amphotericin B-Loaded microparticles

Publication date: Available online 17 June 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Ariane J. Sousa-Batista, Wallace Pacienza-Lima, Maria Inês Ré, Bartira Rossi-BergmannAbstractThe development of an effective amphotericin B (AmB) topical formulation to replace the systemically toxic injections currently used in cutaneous leishmaniasis (CL) treatment is challenging due to poor absorption through the skin. Aiming at an effective local chemotherapy, we designed PLGA (poly lactide-co-glycolide acid) microspheres loaded with deoxycholate amphotericin B (d-AmB) for both macrophage intracellular targeting and sustained extracellular release. For that, d-AmB/PLGA microspheres with sizes ranging from 0.5 μm to 20 μm were synthesized and tested both in vitro and in vivo. In vitro, d-AmB/PLGA was more selectively active against intracellular amastigotes of Leishmania amazonensis than free d-AmB (selectivity index = 50 and 25, respectively). In vivo, the efficacy of a single intralesional (i.l) injection with d-AmB/PLGA was determined in early and established BALB/c mouse ear lesions. In early lesions, a single injection given on day 10 of infection was more effective in controlling parasite growth than eight i.l. injections with free d-AmB, as measured on day 120. Such d-AmB/PLGA injection was also effective in established lesions (day 30), leading to 97% parasite burden reduction, as compared with d-AmB or liposomal AmB (Ambiso...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research