Depot Subcutaneous Injection with Chalcone CH8-Loaded Poly(Lactic-Co-Glycolic Acid) Microspheres as a Single-Dose Treatment of Cutaneous Leishmaniasis.

Autor:	Sousa-Batista AJ; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Pacienza-Lima W; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Arruda-Costa N; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Falcão CAB; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Ré MI; Université de Toulouse, Mines Albi, CNRS, Centre Rapsodee, Campus Jarlard, F-81013 Albi Cedex 09, France., Rossi-Bergmann B; Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil bartira@biof.ufrj.br.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2018 Feb 23; Vol. 62 (3). Date of Electronic Publication: 2018 Feb 23 (Print Publication: 2018).
DOI:	10.1128/AAC.01822-17
Abstrakt:	Conventional chemotherapy of cutaneous leishmaniasis (CL) is based on multiple parenteral or intralesional injections with systemically toxic drugs. Aiming at a single-dose localized therapy, biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with 7.8% of an antileishmanial nitrochalcone named CH8 (CH8/PLGA) were constructed to promote sustained subcutaneous release. In vitro , murine macrophages avidly phagocytosed CH8/PLGA smaller than 6 μm without triggering oxidative mechanisms. Upon 48 h of incubation, both CH8 and CH8/PLGA were 40 times more toxic to intracellular Leishmania amazonensis than to macrophages. In vivo , BALB/c were given one or three subcutaneous injections in the infected ear with 1.2 mg/kg of CH8 in free or CH8/PLGA forms, whereas controls received three CH8-equivalent doses of naked PLGA microparticles or meglumine antimoniate (Glucantime; Sanofi-Aventis). Although a single injection with CH8/PLGA reduced the parasite loads by 91%, triple injections with free CH8 or CH8/PLGA caused 80 and 97% reductions, respectively, in relation to saline controls. Meglumine antimoniate treatment was the least effective (only 36% reduction) and the most toxic, as indicated by elevated alanine aminotransferase serum levels. Together, these findings show that CH8/PLGA microparticles can be effectively and safely used for single-dose treatment of CL. (Copyright © 2018 American Society for Microbiology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu