A Formulation of Paromomycin Sulphate as a Promising Fucose-Conjugated Nanostructured Lipid Carrier for Antileishmanial Drug Delivery.

Abstract

Environmental and individual risk factors make leishmaniasis an important public health problem. Presently, there are several medicines existing for the cure of leishmaniasis, but a major problem associated with them is their adverse effects. The affinity to the fucose receptor increases the phagocytosis of ligand-bound carriers and simultaneously targets the delivery of the antileishmanial agent. Paromomycin sulphate-bearing nanostructured lipid carriers (NLCs) were formulated by a double emulsion solvent evaporation technique, and then chemistry of ring opening trailed by the reaction of fucose's aldehyde groups was analyzed for conjugation. The NLCs and conjugated-NLCs were examined in terms of average size, entrapment efficiency of drugs, polydispersity index, zeta potential, and in vitro drug release. Hemolytic toxicity was measured on whole human blood, and percent hemolysis by drug-loaded fucosylated-NLCs is reduced from 21.09 ± 1.5% to 5.81 ± 0.9 compared to the plain drug. Macrophage uptake of fluorescein isothiocyanate (FITC)-loaded plain NLCs and fucosylated-NLCs showed that mean FITC measured intensity increases in macrophage cell lines. MTT cytotoxicity assay ensured that NLCs could be beneficial as a biocompatible drug carrier for biomedical and pharmaceutical use. BALB/c mice were used for in vivo studies. Qualitative uptake of fucosylated-NLCs was observed by fluorescence microscopy, and the access of fucosylated-NLCs to the liver was revealed. Similar results were obtained by biodistribution studies. Therefore, fucose-conjugated nanoparticulate carriers can be designed to target macrophages with antileishmanial agents against the Leishmania parasite.