Nanoparticles of star-like copolymer mannitol-functionalized poly(lactide)-vitamin E TPGS for delivery of paclitaxel to prostate cancer cells

Abstract

The purpose of this research was to develop novel nanoparticles (NPs) of star-like copolymer mannitol-functionalized poly(lactide)-vitamin E TPGS (M-PLA-TPGS) for paclitaxel delivery for prostate cancer treatment, and evaluate their therapeutic effects in prostate cancer cell line and animal model in comparison with the linear PLGA NPs and poly(lactide)-vitamin E TPGS (PLA-TPGS) NPs. The paclitaxel-loaded M-PLA-TPGS NPs, prepared by a modified nano-precipitation method, were observed by FESEM to be near-spherical shape with narrow size distribution. The drug-loaded NPs were further characterized in terms of size, surface charge, drug content, encapsulation efficiency and in vitro drug release. The results showed that the M-PLA-TPGS NPs were found to be stable, showing almost no change in particle size and surface charge during the three-month storage period. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release. The cellular uptake level of M-PLA-TPGS NPs was demonstrated higher than linear PLGA NPs and PLA-TPGS NPs in PC-3 cells. The data also showed that the paclitaxel-loaded M-PLA-TPGS nanoparticles have higher antitumor efficacy than that of linear PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In summary, the star-like copolymer M-PLA-TPGS could be used as a potential and promising molecular biomaterial in developing novel nanoformulation for prostate cancer treatment.