Development and Optimization of Capecitabine Loaded Nanoparticles for Colon Cancer Therapy

Abstract

The goal of this study was to develop and optimize the Capecitabine loaded chitosan nanoparticles (CS-NPs)for improved colon cancer therapy, by enhancedsurface area, sustained drug release, reduced dose and hence, most importantly, reduced toxicity. Capecitabine loaded Chitosan nanoparticles were prepared by 32 full factorial designs, using ionotropic gelation method by crosslinking of chitosan (CS) with sodium tripolyphosphate (TPP). CS-NPs were prepared by dissolving chitosan in 1% (w/v) acetic acid solution under magnetic stirring at room temperature. The CS solution was diluted with deionized water to produce different concentration. The capecitabine was dissolved in CS solution using sonication and aqueous TPP solution was added drop wise using syringe to the mixture with moderate stirring for 30 min. The prepared nanoparticles were characterized by FT-IR spectroscopy and DSC to confirm the cross linking reaction between CS and cross-linking agent. From the % entrapment of capecitabine, nanoparticles were optimized using regression analysis, contour plots and check point analysis.Particle size of the optimized batch (CS-NPs-8) was found to be 87 nm. The Polydispersity index of the nanoparticles was found to be 0.113. The nanoparticles formed were spherical in shape with high zeta potentials, -35mV. In vitro release studies in phosphate buffer saline (pH 7.4) showed an initial burst effect and followed by a slow drug release. The drug release followed first order kinetics and was found to be diffusion controlled. Optimized formulation was also showing more % inhibition than drug alone in In-vitro anticancer study. From the accelerated study of optimized batch, it was found to be stable.