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用于生物医学应用的活性泊洛沙姆407的合成与表征

Synthesis and characterization of reactive poloxamer 407s for biomedical applications.

作者信息

Niu Guoguang, Du Fengyi, Song Li, Zhang Hongbin, Yang Jun, Cao Hui, Zheng Yudong, Yang Zhou, Wang Guojie, Yang Huai, Zhu Siquan

机构信息

School of Materials Science and Engineering, University of Science and Technology, Beijing, China.

出版信息

J Control Release. 2009 Aug 19;138(1):49-56. doi: 10.1016/j.jconrel.2009.04.026. Epub 2009 May 4.

Abstract

The drawbacks of poloxamer hydrogel, such as dissolving quickly in aqueous solution, have limited its biomedical application. In order to improve the stability of hydrogel, a novel system was developed by combining the reversible thermo-sensitive property of poloxamer 407 and the thiol-ene reactivity between the acrylate and thiol groups. It was found that the sol-gel transition of the acrylate/thiol modified poloxamer 407 mixture could be achieved at body temperature even with a low concentration of 17.5 wt.%. Meanwhile, the reaction between the acrylate and thiol modified poloxamer 407s occurred spontaneously in mimic physiological conditions, thus the hydrogel with crosslinking structure was formed. As a result, the stability of the crosslinked hydrogel was enhanced remarkably, and the release time of the drug from the crosslinked hydrogel was about 4.0 times as long as that from the poloxamer 407 hydrogel. Invitro and invivo experiments revealed that the biocompatibilities of the modified poloxamer 407 hydrogel were similar to that of poloxamer 407. These results indicate that the modified poloxamer 407s have potential applications in controlled drug release, tissue engineering and cell encapsulation etc.

摘要

泊洛沙姆水凝胶存在一些缺点,比如在水溶液中溶解迅速,这限制了其在生物医学领域的应用。为了提高水凝胶的稳定性,通过结合泊洛沙姆407的可逆热敏特性以及丙烯酸酯基团和硫醇基团之间的硫醇-烯反应活性,开发了一种新型体系。研究发现,即使在低浓度17.5 wt.%的情况下,丙烯酸酯/硫醇改性的泊洛沙姆407混合物在体温下也能实现溶胶-凝胶转变。同时,丙烯酸酯改性的泊洛沙姆407和硫醇改性的泊洛沙姆407之间的反应在模拟生理条件下自发发生,从而形成了具有交联结构的水凝胶。结果,交联水凝胶的稳定性显著提高,药物从交联水凝胶中的释放时间约为从泊洛沙姆407水凝胶中释放时间的4.0倍。体外和体内实验表明,改性泊洛沙姆407水凝胶的生物相容性与泊洛沙姆407相似。这些结果表明,改性泊洛沙姆407在药物控释、组织工程和细胞封装等方面具有潜在应用。

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