Amphotericin B-loaded mannose modified poly(d,l-lactide-co-glycolide) polymeric nanoparticles for the treatment of visceral leishmaniasis: in vitro and in vivo approaches

Abstract

It is evident from many previous research works that the mannose receptors on the surface of macrophages play an important role in the process of phagocytosis and they are over-expressed in some intracellular parasitic diseases like leishmaniasis. Toxicity and drug resistance were the major drawbacks in the treatment of visceral leishmaniasis in the past. To overcome these setbacks we have developed amphotericin B-loaded mannose modified PLGA nanoparticles. O-Stearoyl mannose was synthesized and used to prepare mannose modified PLGA nanoparticles. FTIR and DSC analyses were carried out to determine the drug–excipient compatibility and particle size, and SEM and TEM studies were carried out to determine the physicochemical characteristics of the formulated nanoparticles. An in vitro cumulative drug release study for the formulated nanoparticles was carried out, showing the release of amphotericin B in a controlled manner for a prolonged period of time. From the ex vivo cellular uptake study it was observed that the rate of intracellular internalization was significantly higher for the mannose-modified nanoparticles than for the unmodified ones. Selectivity indexes were calculated to determine the antileishmanial efficiency in the in vitro cellular amastigote model, and were almost 4 fold higher for the mannose modified formulation than for the free amphotericin B. A mice model was used for an in vivo study, showing a 98.19% ± 0.33% suppression of the amastigote burden in the spleen. So, it could be concluded that amphotericin B-loaded mannose modified PLGA nanoparticles are more efficacious in the treatment of visceral leishmaniasis in both in vitro and in vivo models than unmodified nanoformulations.