Oral amodiaquine microparticles repurposed for the treatment of visceral leishmaniasis

Background: Leishmaniasis, a neglected tropical disease, is caused by parasites from the genus Leishmania and transmitted by the female phlebotamine sandfly. Visceral leishmaniasis is the systemic and most severe form of the disease, which is brought on by Leishmania donovani and Leishmania infantum complexes. Current treatment options have been plagued with a number of adverse effects, and resistance by the protozoan parasite (Leishmania spp). Following current trends of repurposing drugs, oral formulations of amodiaquine - an antimalarial drug, are tested in visceral leishmaniasis models. Methods: Modified-release formulations of Amodiaquine were prepared by encapsulation in Hydroxypropylmethylcellulose using the spray-drying method and evaluated for size, zeta potential, drug content, entrapment efficiency and in vitro release properties. Mice models were created by infection with stationary phase L. donovani promastigotes. Three weeks after infection, mice were treated by orally administering amodiaquine powder or microparticles for two weeks. Amphotericin B and Pentamidine were administered intraperitoneally as Positive Controls and water given orally as a Negative Control. Giemsa-stained histological sections of mice liver and spleen were prepared and observed for parasite presence and drug activity. Results: The size range of the amodiaquine microparticles was between 2.01 and 15.9 µm and encapsulation efficiency of 95%. The release of amodiaquine from the microparticles was effectively extended. All three formulations of amodiaquine used were effective in treating the visceral leishmaniasis mouse model used in the study. Conclusion: Amodiaquine, an anti-malarial drug, can be repurposed in all oral formulations for the safe and effective treatment of visceral leishmaniasis.