Chitosan-titanium dioxide-glucantime nanoassemblies effects on promastigote and amastigote of Leishmania major.

The purpose of the present study was to design nanoassemblies of chitosan-titanium dioxide (TiO2) nanoparticles (NPs) loaded with glucantime for using their synergistic effects and enhancing the toxic effects of glucantime on Leishmania parasites. The nanoassemblies were prepared by electrostatic interactions and optimized by a response surface central composite design. The effects of glucantime, chitosan and TiO2 NPs amounts were studied on the particle size, zeta potential, loading efficiency, and release efficiency of drug from nanoassemblies. The conjugation of TiO2/chitosan-glucantime was verified by UV spectroscopy and changes in surface charge of NPs. The anti-promastigots effect of glucantime loaded in TiO2/chitosan nanoassemblies was studied by tripan blue dye test and their anti-amastigotes effect by counting the average number of parasites per infected J774 macrophages in 100 cells. The optimized formulation obtained by using 12.5mg glucantime, 25mg chitosan and 6mg TiO2 NPs. Although TiO2 NPs alone were effective more than negative control in reduction of promastigots and amastigotes but they didn't show significant difference compared with free glucantime (p>0.05). However, at the concentration of 50μg/mL and after 72h exposure nanoassemblies decreased the proliferation of L. major promastigotes and amastigotes 13 and 4-fold, respectively compared with glucantime alone.