期刊
JOURNAL OF CONTROLLED RELEASE
卷 161, 期 1, 页码 124-131出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2012.04.010
关键词
Polymers; PGG copolymer; Subcellular trafficking; Drug release; Drug delivery; Physicochemical characteristics
Polymeric prodrugs are one of the most promising chemotherapeutic agent delivery approaches, displaying unique drug release profiles, serum stability, formulation flexibility, and reduced drug resistance. One of the most important aspects of a polymeric prodrug, albeit a less-extensively studied one, is the polymer's molecular weight, which affects particle formation, drug release and PK/PD profiles, drug stability, and cell uptake; these factors in turn affect the prodrug's maximum tolerated dose and anticancer efficacy. Poly(L-gamma-glutamylglutamine) (PGG) is a linear polymer designed to improve the therapeutic index of attached drugs. In this study we selected poly(L-gamma-glutamylglutamine)-paclitaxel (PGG-PTX), as a model system for the methodical investigation into the effects of the poly(L-gamma-glutamylglutamine) backbone molecular weight on its pharmacological performance. The polymeric prodrug was characterized by NMR, DLS and GPC-MALS, and its anticancer activity in vitro and in vivo was assessed. Herein we present data which provide valuable insight into improving anticancer polymer-based prodrug design and development. (C) 2012 Elsevier B.V. All rights reserved.
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