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Nanostructured biopolymers to deliver antimicrobial peptides with leishmanicidal activity

Abstract

Leishmania species infect at least 10 million people worldwide. Cutaneous leishmaniasis, a disease that causes skin ulceration and deformities, has 70% of its global burden concentrated in the Americas, whereas Brasil contributes to more than 12%. Some protozoan species presented resistance to N-Methyl-D-glucamine, the most disseminated treatment for leshmaniasis. It is likely that resistance also occurs for pentamidin, the second choice drug. Nevertheless, resistance studies are laborious, unstandardized and scarce. The antifungal Amphotericin B have not generate resistant Leishmania strains so far, but it presents several relevant side effects and it needs hospitalized administration. Its effect on microbial membranes, similar to antimicrobial peptides, diminish the likelihood of spread resistance. Based on these observations, our laboratory explore the leishmanicidal potential of antimicrobial peptides already approved for human use for other infections. In this context, polymyxin B presented moderate leishmanicidal properties, although highly effective for Pseudomonas strains. However, peptides might have enhanced activity when delivered through nanoformulations, reason why this project aims to develop biopolimeric nanoparticles (chitosan/hyaluronic acid) loaded with polymyxyn. The formulation will be tested in vitro with intracellular and extracellular Leishmania amazonensis. The future goal is a topic application that, if successful, will enhance patient compliance and access to cutaneous leishmaniasis treatment. This is especially helpful in regions far away from hospitals, like the endemic Amazon region. The product can also be tested for other protozoa species and gender, while the technique can be applied to other lipopeptides. These possibilities justify future projects that could establish a new research line for Instituto de Medicina Tropical da USP, a reference institute for neglected diseases. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIBEIRO COSTA, JULIANA SOUZA; MEDEIROS, MARILIA; YAMASHIRO-KANASHIRO, EDITE HARUMI; ROCHA, MUSSYA CISOTTO; COTRIM, PAULO CESAR; STEPHANO, MARCO ANTONIO; LANCELLOTTI, MARCELO; TAVARES, GUILHERME DINIZ; OLIVEIRA-NASCIMENTO, LAURA. Biodegradable nanocarriers coated with polymyxin B: Evaluation of leishmanicidal and antibacterial potential. PLoS Neglected Tropical Diseases, v. 13, n. 5 MAY 2019. Web of Science Citations: 0.
PACHIONI-VASCONCELOS, JULIANA DE ALMEIDA; LOPES, ANDRE MORENI; APOLINARIO, ALEXSANDRA CONCEICAO; VALENZUELA-OSES, JOHANNA KARINA; RIBEIRO COSTA, JULIANA SOUZA; NASCIMENTO, LAURA DE OLIVEIRA; PESSOA, JR., ADALBERTO; SOUZA BARBOSA, LEANDRO RAMOS; RANGEL-YAGUI, CARLOTA DE OLIVEIRA. Nanostructures for protein drug delivery. BIOMATERIALS SCIENCE, v. 4, n. 2, p. 205-218, 2016. Web of Science Citations: 25.

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