Macrophage ghost entrapped amphotericin B: a novel delivery strategy towards experimental visceral leishmaniasis

Abstract

Leishmania donovani, an intracellular parasite, poses many challenges against attempted chemotherapy. After the resistance towards the first-line antileishmanial drug, amphotericin B has become the treatment of choice against visceral leishmaniasis, a fatal tropical disease. However, unfavorable toxicity profile, severe side effects, and prolonged parenteral administration limit its use. Lack of available specific delivery system also makes this drug unsafe for long-term use. In the current study, a "ghost cell" strategy based on macrophage membrane-derived nanovesicle has been introduced as a specific carriage for amphotericin B. Membrane proteins of macrophage ghost play a crucial role in the dissemination of infection in host by communicating between infected neutrophil-macrophage system and non-infected macrophages. These membrane proteins are the basis of specificity of the drug delivery to the infected tissues in this current macrophage ghost cell carrier. This cheap and biocompatible delivery vehicle has significantly improved the toxicity profile and lowered LD50 value of the drug compared to traditional way of its direct administration and widely accepted antileishmanial therapy, AmBisome.

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