Improved efficacy of meglumine antimoniate incorporated in anionic liposomes against Leishmania infantum infecting canine macrophages

Autor(es)

Ortega, Vanessa ; Radaic, Allan ; de Jesus, Marcelo Bispo ; de Paula, Eneida ; Giorgio, Selma

• Tipo de documento: Artigo Científico
• Fonte: Journal of Pharmacy and Pharmacology; v. 74, n. 6, p. 9-pg., 2021-07-21.

Resumo

Objectives Leishmaniasis is a zoonotic disease and several drugs have been used in the treatment, including meglumine antimoniate (AME). The chemotherapy reaches clinical cure but does not eliminate parasites, contributing to drug resistance. To improve AME efficacy we incorporated it in anionic liposomes. The antiparasitic activity and intracellular localization were investigated in canine macrophages infected with Leishmania infantum. Methods Liposomes (L-AME) is composed of egg phosphatidylcholine, cholesterol, palmitoyl oleoyl phosphatidyl serine and alpha-tocopherol (4 : 3 : 0.4 : 0.07 mol%) plus AME. L-AME size, polydispersity, zeta potential and morphology were analysed as well as antileishmanial activity and intracellular localization in DH82 macrophages. Key findings Liposomes (360 nm) zeta potential range from -40 to -65 mV, had 23% encapsulation efficiency and were stable for 180 days at 4 degrees C. Free AME was cytotoxic towards L. infantum infected macrophages (ID50 = 0.012 M) while L-AME did not reduce cell viability. L-AME colocalized with parasites inside macrophages in a time-dependent manner, and reduced the percentage of infected cells and the number of intracellular parasites, decreasing the infection index (75-80%) twice as compared with AME treatment. Conclusions Liposomal AME is a promising delivery system for treating visceral leishmaniasis, improving meglumine efficacy against L. infantum and minimizing its cytotoxicity towards canine macrophages (AU)

• Processo FAPESP: 14/12443-7 - Desenvolvimento de sistema de duplo carregamento para o antimoniato de meglumina e sua avaliação in vitro em macrófagos infectados com L. infantum
• Beneficiário: Vicky Vanessa Ortega Gaona
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/23767-0 - Pesquisa de biomarcadores e desenvolvimento de linhagens de Leishmania infantum
• Beneficiário: Selma Giorgio
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/01536-1 - Interações Leishmania amazonensis-macrófago: mudanças homeostáticas associadas a super-expressão de HSP70. Perfil celular de lesões leishmanióticas: efeitos de inibidores de Gliceraldeído 3-fosfato desidrogenase
• Beneficiário: Selma Giorgio
• Modalidade de apoio: Auxílio à Pesquisa - Regular