A co-delivery system based on paclitaxel grafted mPEG-b-PLG loaded with doxorubicin: Preparation, in vitro and in vivo evaluation

作者：Li Qian; Lv Shixian; Tang Zhaohui^*; Liu Muhua; Zhang Dawei; Yang Yan; Chen Xuesi

来源：International Journal of Pharmaceutics, 2014, 471(1-2): 412-420.

DOI：10.1016/j.ijpharm.2014.05.065

• Co-delivery
• Doxorubicin
• Paclitaxel
• Poly(L-glutamic acid)
• Human breast cancer

Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin hydrochloride (DOX center dot HCl) based on methoxypoly(ethylene glycol)-block-poly(L-glutamic acid) (mPEG-b-PLG) for cancer treatment. PTX was grafted to the mPEG-b-PLG by esterification to give mPEG-b-PLG-g-PTX. DOX center dot HCl was encapsulated via electrostatic interaction and hydrophobic stack between the DOX center dot HCl and mPEG-bPLG-g-PTX in aqueous solution. The release rate of DOX center dot HCl from the drug-loaded nanoparticles (mPEG-b-PLG-g-PTX-DOX) was slow at blood pH (pH 7.4), but obviously increased at endosome pH (pH 5.4). The mPEG-b-PLG-g-PTX-DOX exhibited slight synergistic effect in inhibition of proliferation of A549 and MCF-7 human cancer cells. For in vivo treatment of xenograft human breast tumor (MCF-7), the mPEG-bPLG-g-PTX-DOX nanoparticles exhibited remarkable tumor inhibition effect with a 95.5% tumor-suppression-rate which was significantly higher than those of related single anticancer agents such as free DOX center dot HCl and mPEG-b-PLG-g-PTX. These results indicated that the mPEG-b-PLG-g-PTX-DOX would have great potential in cancer therapy.

• 出版日期2014-8-25
• 单位江西农业大学; 吉林大学; 中国科学院大学; 中国科学院长春应用化学研究所