Development and optimization of curcumin-loaded mannosylated chitosan nanoparticles using response surface methodology in the treatment of visceral leishmaniasis

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.

Keywords::

• central composite design
• curcumin
• nanoparticles
• optimization
• response surface methodology
• visceral leishmaniasis

Acknowledgements

The authors acknowledge the help of GVS Sastry (Department of Metallurgical Engineering, IIT-BHU), YB. Tripathi (Department of Medicinal Chemistry, Institute of Medical Sciences, BHU) for carrying out SEM and ex vivo studies, respectively. The authors also acknowledge the help of Mukul Gupta, UGC-CSR-Indore, India, in carrying out the PXRD analysis.

Poster Presentation at International Conference on Nanoscience and Nanotechnology (ALIGARH NANO-IV International 2014) held at Aligarh Muslim University, Aligarh, INDIA from 08-10 March, 2014.

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