In Vitro and In Vivo Investigation of Nanoparticles of A Novel Copolymer for Substained and Controlled Delivery of Docetaxel

Abstract

Docetaxel has been found to have high tumor efficacy. However, its current clinical dosage form of Taxotere® is formulated in Polysobate 80 which causes serious side effects. Nanoparticles of biodegradable polymers may provide an ideal solution to such an adjuvant problem, promote sustainable and controlled chemotherapy. Here, we report a novel two-component copolymer: one is poly(lactic acid) (PLA), which is a U.S. FDA approved biodegradable polymer, and another is d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS), which is a PEGylated vitamin E. The docetaxel-loaded PLA-TPGS nanoparticles showed a prolonged drug release profile over a month. Additionally, TPGS-emulsified nanoparticles are smaller in particle size with better drug encapsulation efficiency, higher stability and cellular uptake than that using polyvinyl alcohol (PVA). Also, TPGS-emulsified nanoparticles achieve higher in vitro cytotoxicity compared to PVA-emulsified nanoparticles or Taxotere®. In vivo pharmacokinetics and biodistribution analysis of TPGS-emulsified NPs further demonstrate long systemic circulation effect with lower drug accumulation in various important organs than Taxotere®, thus showing safer and promising formulation for cancer chemotherapy.