Development and characterization of amphotericin B loaded solid lipid nanoparticles against experimental visceral leishmaniasis

Abstract

In the present work amphotericin B (AmB) was formulated in tristearin-based solid lipid nanoparticles (SLNs) stabilized by soya phosphatidylcholine (PC), for macrophage targeting against visceral leishmaniasis (VL). SLNs were modified by coating them with macrophage-specific ligand, O-palmitoyl mannan (OPM). The surface modified and unmodified SLNs were characterised for size, shape, zeta potential and entrapment efficiency. The antileishmanial activity of free and SLNs entrapped AmB was tested in vitro in Leishmania donovani infected macrophage-amastigote system (J774A.1 cells), which showed higher efficacy of OPM grafted AmB-SLNs (SLNs-OPM) over plain AmB-SLNs and free AmB (AmB-Doc). The in-vivo organ distribution studies in albino rats confirmed that degree of accretion of SLNs en-trapped AmB in macrophage rich organs, particularly liver, spleen and lungs was considerably high when compared against AmB-Doc. The rate and degree of accretion were found to increase further on ligand anchoring. The in vivo an-tileishmanial activity of the AmB encapsulated SLNs-OPM was found to be better as compared to SLNs and AmB-Doc against VL in L. donovani infected hamsters. The proposed formulations, SLNs and SLNs-OPM demonstrated tremendous potential for passive and active intramacrophage targeting respectively and the strategy could be a booming alternative to the presently existing drug regimens of VL and systemic fungal infections.