Oral chemotherapy is quickly emerging as an appealing option for cancer patients. It is less stressful because the patient has fewer hospital visits and can still maintain a close relationship with health care professionals. Three kinds of nanoparticles made from commercial poly(epsilon-caprolactone) (PCL) and self-synthesized d--tocopheryl poly(ethylene glycol) 1000 succinate -b-poly(epsilon-caprolactone-ran-glycolide) [TPGS-b-(PCL-ran-PGA)] diblock copolymer were prepared in this study for the oral delivery of antitumor agents, including chitosan-modified PCL nanoparticles, nonmodified TPGS-b-(PCL-ran-PGA) nanoparticles, and chitosan-modified TPGS-b-(PCL-ran-PGA) nanoparticles. First, the TPGS-b-(PCL-ran-PGA) diblock copolymer was synthesized and structurally characterized. Chitosan was adopted to extend the retention time at the cell surface and thus increase the chance of nanoparticle uptake by the gastrointestinal mucosa and improve the absorption of drugs after oral administration. The resulting TPGS-b-(PCL-ran-PGA) nanoparticles were found to be of spherical shape and around 200 nm in diameter with a narrow size distribution. The surface charge of the TPGS-b-(PCL-ran-PGA) nanoparticles could be reversed from anionic to cationic after surface modification. The chitosan-modified TPGS-b-(PCL-ran-PGA) nanoparticles displayed a significantly higher level of cellular uptake compared with the chitosan-modified PCL nanoparticles and nonmodified TPGS-b-(PCL-ran-PGA) nanoparticles. In vitro cell viability studies showed the advantages of the chitosan-modified TPGS-b-(PCL-ran-PGA) nanoparticles over Taxol in terms of their cytotoxicity against human RT112 cells. In summary, the oral delivery of antitumor agents by chitosan-modified TPGS-b-(PCL-ran-PGA) nanoparticles produced results that were promising for the treatment of patients with bladder cancer. (c) 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2118-2126, 2013