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Home / Publicações / Hemisynthetic trifluralin analogues incorporated in liposomes for the treatment of leishmanial infections

Hemisynthetic trifluralin analogues incorporated in liposomes for the treatment of leishmanial infections

  • Autores: Alexandra Esteves M, Armanda Rodrigues M, Carvalheiro M, Cruz MEM, Eleuterio CV, Lopes RM, Santos-Gomes G, Santos-Mateus D, Scoulica E
  • Ano de Publicação: 2015
  • Journal: European Journal of Pharmaceutics and Biopharmaceutics
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/25936854

Leishmaniasis, a vector-borne parasitic disease caused by Leishmania protozoa, is one of the most neglected tropical diseases in terms of drug discovery and development. Current treatment is based on a limited number of chemotherapeutic agents all of which present either/or resistance issues, severe toxicities and adverse reactions associated with extended treatment regimens, and high cost of therapy. Dinitroanilines are a new class of drugs with proven in vitro antileishmanial activity. In previous work a liposomal formulation of one dinitroaniline (TFL) was found to be active against Leishmania parasites in a murine model of visceral leishmaniasis (VL) and in the treatment of experimental canine leishmaniasis. In this study we have investigated the use of dinitroaniline analogues (TFL-A) associated to liposomes, as means to further improve TFL antileishmanial activity. The potential of the liposomal formulations was assessed in vitro against Leishmania infantum promastigotes and intracellular amastigotes and in vivo in a murine model of zoonotic VL. Free and liposomal TFL-A were active in vitro against Leishmania parasites, and they also exhibited reduced cytotoxicity and haemolytic activity. Treatment of infected mice with liposomal TFL-A reduced the amastigote loads in the spleen up to 97%, compared with the loads for untreated controls. These findings illustrate that chemical synthesis of new molecules associated with the use of Nano Drug Delivery Systems that naturally target the diseased organs could be a promising strategy for effective management of VL.

Hemisynthetic trifluralin analogues incorporated in liposomes for the treatment of leishmanial infections

  • Autores: Alexandra Esteves M, Armanda Rodrigues M, Carvalheiro M, Cruz MEM, Eleuterio CV, Lopes RM, Santos-Gomes G, Santos-Mateus D, Scoulica E
  • Ano de Publicação: 2015
  • Journal: European Journal of Pharmaceutics and Biopharmaceutics
  • Link: http://www.ncbi.nlm.nih.gov/pubmed/25936854

Leishmaniasis, a vector-borne parasitic disease caused by Leishmania protozoa, is one of the most neglected tropical diseases in terms of drug discovery and development. Current treatment is based on a limited number of chemotherapeutic agents all of which present either/or resistance issues, severe toxicities and adverse reactions associated with extended treatment regimens, and high cost of therapy. Dinitroanilines are a new class of drugs with proven in vitro antileishmanial activity. In previous work a liposomal formulation of one dinitroaniline (TFL) was found to be active against Leishmania parasites in a murine model of visceral leishmaniasis (VL) and in the treatment of experimental canine leishmaniasis. In this study we have investigated the use of dinitroaniline analogues (TFL-A) associated to liposomes, as means to further improve TFL antileishmanial activity. The potential of the liposomal formulations was assessed in vitro against Leishmania infantum promastigotes and intracellular amastigotes and in vivo in a murine model of zoonotic VL. Free and liposomal TFL-A were active in vitro against Leishmania parasites, and they also exhibited reduced cytotoxicity and haemolytic activity. Treatment of infected mice with liposomal TFL-A reduced the amastigote loads in the spleen up to 97%, compared with the loads for untreated controls. These findings illustrate that chemical synthesis of new molecules associated with the use of Nano Drug Delivery Systems that naturally target the diseased organs could be a promising strategy for effective management of VL.

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