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  • Title: Development and optimization of curcumin-loaded mannosylated chitosan nanoparticles using response surface methodology in the treatment of visceral leishmaniasis.
    Author: Chaubey P, Patel RR, Mishra B.
    Journal: Expert Opin Drug Deliv; 2014 Aug; 11(8):1163-81. PubMed ID: 24875148.
    Abstract:
    OBJECTIVE: The study aims at formulation and optimization of macrophage-targeted curcumin-loaded mannosylated chitosan nanoparticles (Cur-MCNPs) of curcumin (CUR) to improve its therapeutic potential in the treatment of visceral leishmaniasis (VL). METHODS: Response surface methodology (RSM) using central composite design was employed to study the effect of formulation factors on physicochemical-dependent characteristics. Chitosan was coupled with d-mannose, by reductive amination, to prepare a mannosylated chitosan, a conjugate polymer and a subsequent formulation of Cur-MCNPs. Optimized formulation prepared using RSM was evaluated for in vitro release kinetics at physiological pH 7.4 and endosomal macrophage pH 4.5; in vivo pharmacokinetic profile and targeting potential were evaluated by fluorescence microscopy. RESULTS: Optimized Cur-MCNPs exhibited spherical and smooth surface with a mean particle size of 215 nm, polydispersity index of 0.381, zeta potential of + 24.37 mV and % entrapment efficiency of 82.12%. The pharmacokinetic study of optimized Cur-MCNPs showed significant improvement in the value of mean resident time (39.38 h) compared to free CUR solution (0.30 h) (p < 0.05). In vivo uptake study indicated that endocytosis took place effectively within the macrophages of reticuloendothelial system. CONCLUSIONS: Thus, Cur-MCNPs could be considered as a promising delivery strategy towards active targeting of CUR to macrophages for the effective treatment of VL.
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