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Characterization of hematin anhydride as a carrier of the drugs miltefosine and paromomycin: leishmanicidal effect in vitro

Grant number: 20/13688-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): March 01, 2021
Effective date (End): February 28, 2022
Field of knowledge:Agronomical Sciences - Veterinary Medicine - Preventive Veterinary Medicine
Principal Investigator:Marina Tiemi Shio
Grantee:Paloma Angela de Souza
Home Institution: Universidade de Santo Amaro (UNISA). São Paulo , SP, Brazil

Abstract

The use of nanoparticles for drug delivery has advantages over conventional chemotherapy, such as releasing the drug at the infection site in a controlled and sustained manner, minimizing the systemic effect and reducing the frequency of administration. Leishmaniasis is a neglected disease that extends to almost the entire Brazilian territory and is caused by protozoa of the genus Leishmania. These parasites are transmitted by sand flies that inject promastigotes forms during blood meal. The parasites are phagocyted by neutrophils, dendritic cells and macrophages. Intracellularly, promastigotes differ in amastigotes, a replicative form of the parasites. Macrophages produce several microbicidal molecules such as nitric oxide (NO) and tumor necrosis factor (TNF). However, in infected macrophages the production of these anti-microbicidal factors is inhibited by several mechanisms.In relation to the treatment of leishmaniasis, in Brazil, the drugs of first choice for treatment in humans are meglumine antimoniate and sodium stibogluconate, these drugs are administered intramuscularly or intravenously and can cause adverse reactions such as renal, hepatic, pancreatic or cardiac problems. The second-choice drugs are amphotericin B, pentamidine, miltefosine and paromomycin. Miltefosine was incorporated into the public network for the oral treatment of cutaneous leishmaniasis and is also the only medication allowed for the treatment of dogs, which are the reservoirs of the parasite. The treatment of leishmaniasis is still a challenge due to the high cost of drugs, high dose of drugs, incidence and prevalence of drug resistance. Thus, there is a need for research into new antibiotic delivery systems, especially for the intracellular environment, which can decrease the dose of the drug, improve its activity in environments with different pH and permeability to the cell membrane. This project aims to evaluate the leishmanicidal capacity of the miltefosine and paromomycin drugs incorporated in hematin anhydride in in vitro experiments with macrophage cell lines infected with the parasite, Leishmania amazonensis.