期刊
JOURNAL OF CONTROLLED RELEASE
卷 151, 期 3, 页码 295-301出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2011.01.017
关键词
Polyglycerol; Drug delivery; Polymer therapeutics; Doxorubicin; Prodrug
资金
- Ministry of Science [BMBF 03X5501]
In an attempt to explore the potential of dendritic systems for the development of effective anticancer drug delivery systems, we explored a simple modular approach of preparing polyglycerol doxorubicin prodrugs, with flexibility for drug loading using an acid-sensitive hydrazone linker and further post-modification with poly(ethylene glycol) shell. The resulting drug polymer conjugates showed optimal properties for in vitro and in vivo applications because of their high water solubility, an appropriate size for passive tumor targeting, a high stability at physiological conditions, pronounced acid-sensitive properties, cellular internalization, and a favorable toxicity profile. Doxorubicin polyglycerol conjugates with a high drug loading ratio showed clearly improved antitumor efficacy over doxorubicin in an ovarian xenograft tumor model (A2780) inducing transient complete remissions thus demonstrating the potential of developing efficient multifunctional dendritic drug delivery using our modular approach. (C) 2011 Elsevier B.V. All rights reserved.
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