期刊
BIOMATERIALS SCIENCE
卷 1, 期 4, 页码 411-420出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/c2bm00159d
关键词
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资金
- Chinese Ministry of Science and Technology (973 Programs) [2009CB930000, 2011CB606203]
- NSF of China [50903021, 21034002, 91127028]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20090071120014]
This study is aimed at extending a thermo-induced physical hydrogel as a localized delivery system of the antitumor drug doxorubicin (DOX). An amphiphilic triblock copolymer consisting of poly(lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) was synthesized. The PLGA-PEG-PLGA triblock copolymer/water system exhibited a reversible sol-gel transition with increasing temperature, and the gel window covered the physiological temperature (37 degrees C). After a subcutaneous injection of the aqueous polymer solution into Sprague-Dawley rats, in situ gelling occurred, and the gel persisted over 20 days in the body. The addition of DOX did not alter the basic thermogelling property, yet our rheological measurements revealed that the increased viscosity of the sol state influenced the available drug concentration, which should be taken into consideration with respect to the injectability. Despite being a small molecule and a water-soluble drug, DOX with an appropriate drug concentration was released from the physical hydrogel in a sustained manner following an initial burst. To evaluate antitumor efficacy in vivo, the formulation was injected subcutaneously into mice bearing sarcoma-180 solid tumors. A single injection of the DOX-loading gel presented higher therapeutic efficacy and lower toxic effects compared to two injections of free DOX under the same total dose.
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