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Type: Artigo
Title: Biodegradable nanocarriers coated with polymyxin B: evaluation of leishmanicidal and antibacterial potential
Author: Costa, Juliana Souza Ribeiro
Medeiros, Marilia
Yamashiro-Kanashiro, Edite Harumi
Rocha, Mussya Cisotto
Cotrim, Paulo Cesar
Stephano, Marco Antonio
Lancellotti, Marcelo
Tavares, Guilherme Diniz
Oliveira-Nascimento, Laura
Abstract: Most treatments of leishmaniasis require hospitalization and present side effects or parasite resistance; innovations in drug formulation/reposition can overcome these barriers and must be pursued to increase therapeutic alternatives. Therefore, we tested polymyxin B (polB) potential to kill Leishmania amazonensis, adsorbed or not in PBCA nanoparticles (PBCAnp), which could augment polB internalization in infected macrophages. PBCAnps were fabricated by anionic polymerization and analyzed by Dynamic Light Scattering (size, potential), Nanoparticle Tracking Analysis (size/concentration), vertical diffusion cell (release rate), drug incorporation (indirect method, protein determination) and in vitro cell viability. Nanoparticles coated with polB (PBCAnp-polB) presented an adequate size of 261.5 25.9 nm, low PDI and of 1.79 +/- 0.17 mV (stable for 45 days, at least). The 50% drug release from PBCAnp-polB was 6-7 times slower than the free polB, which favors a prolonged and desired release profile. Concerning in vitro evaluations, polB alone reduced in vitro amastigote infection of macrophages (10 g/mL) without complete parasite elimination, even at higher concentrations. This behavior limits its future application to adjuvant leishmanicidal therapy or antimicrobial coating of carriers. The nanocarrier PBCAnp also presented leishmanicidal effect and surpassed polB activity; however, no antimicrobial activity was detected. PolB maintained its activity against E. coli, Pseudomonas and Klebsiella, adding antimicrobial properties to the nanoparticles. Thus, this coated drug delivery system, described for the first time, demonstrated antileishmanial and antimicrobial properties. The bactericidal feature helps with concomitant prevention/treatment of secondary infections that worst ulcers induced by cutaneous L. amazonensis, ultimately ending in disfiguring or disabling lesions. Author summary Cutaneous leishmaniasis form disfiguring lesions that leads to depression and social isolation. Both consequences result often in economic and education loss for communities already short on resources. The actual treatment aims to eliminate the protozoa disease-vector. Yet, it presents undesired effects or parasite resistance, besides the need for intravenous infusions and hospitalization. There is a few topical leishmanicidals but none with prolonged action. As highlighted, no ideal therapy exists; we must keep searching for alternatives, which includes new drugs, vehicles or therapies. For drugs, the most cost-effective way comprises testing approved molecules for other diseases, such as the antimicrobial polymyxin B (polB). Repositioning a drug has the added benefit of known safety profile and drawbacks, shortening and narrowing the research path. In turn, carriers can decrease side-effects and multiple dosing. They shield and/or improve drug targeting, which in this case means delivering inside macrophages infected with Leishmania. An example is poly (n-butyl cyanoacrylate) nanoparticles (PBCAnp), shown as an efficient carrier for targeting an extended drug release. Therefore, this work aimed to evaluate leishmanicidal and adjuvant properties of polB, alone and absorbed onto PBCAnp
Subject: Nanocarreadores de fármacos
Polimixina B
Country: Estados Unidos
Editor: Public Library of Science
Rights: Aberto
Identifier DOI: 10.1371/journal.pntd.0007388
Date Issue: 2019
Appears in Collections:IB - Artigos e Outros Documentos
FCF - Artigos e Outros Documentos

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