Abstract

ObjectiveTo assess the efficacy of a novel formulation of the polyene antibiotic, amphotericin B (AMB), as therapy for cutaneous leishmaniasis in different mouse strains.Methods(AMB), was formulated into water-soluble transport particles, termed nanodisks (ND). Balb/c and CH3 mice infected with Leishmania major on Day 0 were administered vehicle alone, empty ND or AMB-ND on Day 1 and day 7, via the tail vein. Mice were sacrificed 25 or 50 days post inoculation and tissue histology evaluated. Balb/c mice treated with vehicle or empty ND showed signs of severe infection while CH3 mice had less inflammation and fewer parasites. AMB-ND treatment (2 mg/kg) had a marked therapeutic effect on L. major infected Balb/c mice and a discernable therapeutic benefit on CH3 mice.ConclusionsAMB-ND is efficacious in the treatment of cutaneous leishmaniasis in both susceptible and resistant mouse strains. It may be inferred that AMB-ND may be useful for prophylactic and/or treatment of early stage Leishmania spp. infection.

Highlights

  • Parasites of the genus Leishmania are intracellular protozoans that infect more than 12 million individuals worldwide, with 400,000 new cases each year

  • Widespread in over 80 countries around the globe, leishmaniasis has been identified as an important medical problem for military personnel serving in endemic regions [1]

  • Sterile filtered (0.22 m) amphotericin B (AMB)-NDs were stored in the dark at 4°C for < 40 days

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Summary

Introduction

Parasites of the genus Leishmania are intracellular protozoans that infect more than 12 million individuals worldwide, with 400,000 new cases each year. Parasites are transmitted to humans via the bite of sand flies (subfamily phlebotomina). These tiny sandcolored, blood-feeding flies breed in forest areas, caves, or the burrows of small rodents. Wild and domesticated animals can serve as a reservoir of infection. Over 20 species and subspecies of Leishmania infect humans, each causing a spectrum of symptoms. These range from simple, self-healing skin ulcers (e.g. infection with L. major) to severe, life-threatening visceral disease (e.g. L_donovani or L. chagasi). Malaise, weight loss and anemia as well as splenomegaly and hepatomegaly in the visceral form

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