A co-delivery system based on paclitaxel grafted mPEG-b-PLG loaded with doxorubicin: Preparation, in vitro and in vivo evaluation
Herein, we develop a co-delivery system of paclitaxel (PTX) and doxorubicin hydrochloride (DOX·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·HCl was encapsulated via electrostatic interaction and hydrophobic stack between the DOX·HCl and mPEG- b -PLG- g -PTX in aqueous solution. The release rate of DOX·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- b -PLG- 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·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.
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