The purpose of the present study was to investigate the therapeutic efficacy of the indigenous
drug arjunglucoside I (AG) against in vivo models of experimental
leishmaniasis by incorporating it in surface hydrophilic co-polymeric
nanogel particles of size less than 100 nm diameter and to compare its efficacy with that of the free
drug as well as the
drug encapsulated in hydrophobic
poly-dl-lactide (PLA) nanoparticles. The
drug AG, having
glucose at the terminal end of the glycosidic chain, was isolated from an indigenous source.
Drug-incorporated ultra-low-sized
nanogels (approximately 90 nm in diameter) composed of cross-linked random co-
polymer of
N-isopropylacrylamide (NIPAAM) and
N-vinyl pyrrolidone(VP) were prepared, characterized and used as delivery vehicles to combat experimental
leishmaniasis in hamster models. For comparison,
drug-encapsulated hydrophobic nanoparticles (approximately 250 nm in diameter) made from PLA were used as a control. The
drug AG was incorporated in these nanocarriers and these
drug-nanocarrier complexes were physically characterized. The efficacy of lowering spleen parasite load by the free
drug, as well as that incorporated in
nanogels and PLA nanoparticles were examined in vivo in equimolar concentration against hamsters undergoing experimental
leishmaniasis. The reduction of
drug toxicity by the
nanogels and PLA nanoparticles was also assessed. The efficacy in the lowering of spleen parasite load with the free
drug was found to be only 38% but was much higher when the
drug was incorporated in co-polymeric
nanogels (79%) or in polymeric nanoparticles (75%). Both the nanocarriers were found to be effective in reducing hepatotoxicity and nephrotoxicity nearly to the same extent. It was apparent that in addition to a smaller size and better drug release profile, the contribution of other parameters, e.g. overall surface hydrophilicity or hydrophobicity of the vehicles, also play an important role in the macrophage uptake of the
drug. However, whatever be the exact mechanism, being highly efficient, non-hepatotoxic and non-nephrotoxic, AG in either of the two nanoparticulate forms may have useful application in humans