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

Author(s)

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

• Document type: Journal article
• Source: Journal of Pharmacy and Pharmacology; v. 74, n. 6, p. 9-pg., 2021-07-21.

Abstract

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)

• FAPESP's process: 14/12443-7 - Development of a double loading system for meglumine antimoniate and its in vitro evaluation in macrophages infected with L. infantum
• Grantee: Vicky Vanessa Ortega Gaona
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/23767-0 - Development of biomarkers and Leishmania infantum strains
• Grantee: Selma Giorgio
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/01536-1 - Leishmania amazonensis-macrophage interactions: homeostatic changes associated with HSP70 overexpression in L. amazonensis cellular profile of leishmaniasis lesions effects of glyceraldehyde 3-phosphate dehydrogenase inhibitors
• Grantee: Selma Giorgio
• Support Opportunities: Regular Research Grants