Drug-Initiated Ring-Opening Polymerization of O-Carboxyanhydrides for the Preparation of Anticancer Drug鈥揚oly(O-carboxyanhydride) Nanoconjugates

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• 作者：Qian Yin ; Rong Tong ; Yunxiang Xu ; Kwanghyun Baek ; Lawrence W. Dobrucki ; Timothy M. Fan ; Jianjun Cheng
• 刊名：Biomacromolecules
• 出版年：2013
• 出版时间：March 11, 2013
• 年：2013
• 卷：14
• 期：3
• 页码：920-929
• 全文大小：561K
• 年卷期：v.14,no.3(March 11, 2013)
• ISSN：1526-4602

文摘

We report a novel synthetic strategy of polymer鈥揹rug conjugates for nanoparticulate drug delivery: hydroxyl-containing drug (e.g., camptothecin, paclitaxel, doxorubicin and docetaxel) can initiate controlled polymerization of phenyl O-carboxyanhydride (Phe-OCA) to afford drug鈥損oly(Phe-OCA) conjugated nanoparticles, termed drug鈥揚heLA nanoconjugates (NCs). Our new NCs have well-controlled physicochemical properties, including high drug loading, quantitative drug loading efficiency, controlled particle size with narrow particle size distribution, and sustained drug release profile over days without 鈥渂urst鈥?release effect as observed in conventional polymer/drug encapsulates. Compared with polylactide NCs, the PheLA NCs have increased noncovalent hydrophobic interchain interactions and thereby result in remarkable stability in human serum with negligible particle aggregation. Such distinctive properties can reduce the premature disassembly of NCs upon dilution in the bloodstream and prolong NCs鈥?in vivo circulation with the enhancement of intratumoral accumulation of NCs, which has a bearing on therapeutic effectiveness.