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This study is intended to develop and evaluate a novel, highly water-soluble polymer drug conjugate poly(l-γ-glutamyl-l-carbocisteine)-paclitaxel (PGSC-PTX) which can trigger drug release in tumor acidic microenvironment and improve the therapeutic index of paclitaxel (PTX). PGSC-PTX is formed by introducing an additional carbocisteine into each glutamic side chain of poly(l-glutamic acid)-paclitaxel (PGA-PTX) conjugate. PGSC-PTX self-assembles into nanoparticles, whose size remains in the range of 15-20nm. PGSC-PTX demonstrated sensitive to pH and released PTX rapidly in low pH. PGSC-PTX shows significant in vitro cytotoxicity to NH460 cancer cell line, which has less toxic and side effect of than PTX. Meanwhile, the hemolytic test indicated that the nanoparticles could be used for intravenous injection. It was concluded that the maximum tolerated dose of PGSC-PTX achieved to be 250mg PTX/kg, which is extremely maximum tolerated providing a significant foundation in the clinical research.
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| http://dx.doi.org/10.1016/j.msec.2017.07.032 | DOI Listing |
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