Abstract
Macrophage targeting therapies are a promising approach to treat various intracellular infections like AIDS, tuberculosis and leprosy. The present paper demonstrates the design and development of mannosylated nanoparticles of biopolymeric origin. Spherical and smooth gelatin nanoparticles in the size range of 100-200 nm with a narrow polydispersity index ( < 0.1) were synthesized and characterized by TEM, AFM and XPS for their morphology and mannosylation. Cell uptake studies by spectrofluorimetry in J774 macrophage cell-line demonstrate two-fold greater internalisation of mannosylated gelatin nanoparticles (MGNP) through macrophage mannose-receptor, than unconjugated nanoparticles (GNP); enhanced uptake of MGNP in J774 macrophages was confirmed by laser confocal microscopy. Evaluation of cellular toxicity by MTT assay reveals close to 100% cell viability confirming biocompatibility. In addition, neither MGNP nor GNP caused ROS (reactive oxidative species) generation in J774 cells. Biodistribution studies in murine model showed significant uptake of MGNP by reticuloendothelial system as early as 15 min after intravenous administration (spleen 0.99±0.14 percent injected dose/100 mg tissue; liver, 1.04±0.11 percent dose/100 mg). The anti-HIV drug stavudine was loaded to 38.2% entrapment efficiency in MGNP and showed 77.5% release in 96 h. Thus, these mannosylated nanoparticles appear to be a very useful carrier system for receptor-specific drug delivery in treatment of macrophage-mediated intracellular infections.
Keywords: Macrophage targeting, gelatin nanoparticles, mannosylation, biocompatibility, in vitro uptake, biodistribution
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