Anti-tumor activity of paclitaxel-loaded chitosan nanoparticles: An in vitro study

Chitosan nanoparticles containing the anticancer drug paclitaxel were prepared by a solvent evaporation and emulsification crosslinking method. The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 116 +/- 15 nm with high encapsulation efficiencies (EE) were obtained. Additionally, a sustained release of paclitaxel from paclitaxel-loaded chitosan nanoparticles was successful. Using different ratios of paclitaxel-to-chitosan, the EE ranged from 32.2 +/- 8.21% to 94.0 +/- 16.73%. The drug release rates of paclitaxel from the nanoparticles were approximately, 26.55 +/- 2.11% and 93.44 +/- 10.96% after 1 day and 13 days, respectively, suggesting the potential of the chitosan nanoparticles as a sustained drug delivery system. cytotoxicity tests showed that the paclitaxel-loaded chitosan had higher cell toxicity than the individual paclitaxel and confocal microscopy analysis confirmed excellent cellular uptake efficiency. TEM images showed the ultrastructure changes of A2780 cells incubated with paclitaxel-loaded nanoparticles. Flow cytometric analysis revealed two subdiploid peaks for the cells in the paclitaxel-loaded nanoparticles and paclitaxel treated groups, respectively, with the intensity of the former higher than that of the latter. Moreover, the cell cycle was arrested in the G(2)-M phase, which was consistent with the action mechanism of the direct administration of paclitaxel. These results indicate that chitosan nanoparticles have potential uses as anticancer drug carriers and also have an enhanced anticancer effect. (C) 2009 Elsevier B.V. All rights reserved.