Polymer, Vol.51, No.25, 5952-5959, 2010
Nanoparticle formulation of poly(epsilon-caprolactone-co-lactide)-D-alpha-tocopheryl polyethylene glycol 1000 succinate random copolymer for cervical cancer treatment
Cervical cancer remains a critical problem that is second only to breast cancer affecting women worldwide. The objective of this study was to develop formulation of docetaxel-loaded biodegradable poly (epsilon-caprolactone-co-lactide)-D-alpha-tocopheryl polyethylene glycol 1000 succinate (PCL-PLA-TPGS) nanoparticles for cervical cancer chemotherapy. A novel random copolymer, PCL-PLA-TPGS, was synthesized from epsilon-caprolactone, lactide and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization. The obtained polymers were characterized by H-1 NMR, FTIR, GPC and TGA. The docetaxel-loaded PCL-PLA-TPGS nanoparticles were prepared by a modified solvent extraction/evaporation technique and characterized in terms of size and size distribution, morphology, surface charge and physical state of encapsulated docetaxel. Cellular uptake and in vitro cytotoxicity of nanoparticle formulations were done in comparison with commercial formulation Taxotere (R) to investigate the efficacy of PCL-PLA-TPGS nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated with CLSM, demonstrating the coumarin 6-loaded PCL-PLA-TPGS nanoparticles could be internalized by Hela cells. In vitro cancer cell viability experiment showed that judged by IC50, the PCL-PLA-TPGS nanoparticle formulation was found to be more effective in cell number reduction than the Taxotere (R) after 48 h (p < 0.05), 72 h (p < 0.05) treatment. In conclusion, the PCL-PLA-TPGS copolymer could be acted as a novel and promising biologically active polymeric matrix material for nanoparticle formulation in cervical cancer treatment. (C) 2010 Elsevier Ltd. All rights reserved.