Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10159294 | Acta Biomaterialia | 2014 | 11 Pages |
Abstract
A novel methoxy poly(ethylene glycol)-b-poly(l-glutamic acid)-b-poly(l-phenylalanine) (mPEG-b-P(Glu)-b-P(Phe)) triblock copolymer was prepared and explored as a micelle carrier for the co-delivery of paclitaxel (PTX) and cisplatin (cis-diamminedichlo-platinum, CDDP). PTX and CDDP were loaded inside the hydrophobic P(Phe) inner core and chelated to the middle P(Glu) shell, respectively, while mPEG provided the outer corona for prolonged circulation. An in vitro release profile of the PTXÂ +Â CDDP-loaded micelles showed that the CDDP chelation cross-link prevented an initial burst release of PTX. The PTXÂ +Â CDDP-loaded micelles exhibited a high synergism effect in the inhibition of A549 human lung cancer cell line proliferation over 72Â h incubation. For the in vivo treatment of xenograft human lung tumor, the PTXÂ +Â CDDP-loaded micelles displayed an obvious tumor inhibiting effect with a 83.1% tumor suppression rate (TSR%), which was significantly higher than that of a free drug combination or micelles with a single drug. In addition, more importantly, the enhanced anti-tumor efficacy of the PTXÂ +Â CDDP-loaded micelles came with reduced side-effects. No obvious body weight loss occurred during the treatment of A549 tumor-bearing mice with the PTXÂ +Â CDDP-loaded micelles. Thus, the polypeptide-based combination of PTX and CDDP may provide useful guidance for effective and safe cancer chemotherapy.
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Physical Sciences and Engineering
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Authors
Wantong Song, Zhaohui Tang, Mingqiang Li, Shixian Lv, Hai Sun, Mingxiao Deng, Huaiyu Liu, Xuesi Chen,