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Drug-initiated ring-opening polymerization of O-carboxyanhydrides for the preparation of anticancer drug-poly(O-carboxyanhydride) nanoconjugates.

ABSTRACT: We report a novel synthetic strategy of polymer-drug 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-poly(Phe-OCA) conjugated nanoparticles, termed drug-PheLA 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 "burst" 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' in vivo circulation with the enhancement of intratumoral accumulation of NCs, which has a bearing on therapeutic effectiveness.


PROVIDER: S-EPMC3671392 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

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