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用于亲水性模型药物水相包封和控释的可生物降解热响应水凝胶。

Biodegradable thermoresponsive hydrogels for aqueous encapsulation and controlled release of hydrophilic model drugs.

作者信息

Huang Xiao, Lowe Tao Lu

机构信息

Department of Surgery, Pennsylvania State University, 500 University Drive, Hershey, Pennsylvania 17033, USA.

出版信息

Biomacromolecules. 2005 Jul-Aug;6(4):2131-9. doi: 10.1021/bm050116t.

DOI:10.1021/bm050116t
PMID:16004455
Abstract

A series of hydrogels with both thermoresponsive and completely biodegradable properties was developed for aqueous encapsulation and controlled release of hydrophilic drugs in response to temperature change. The hydrogels were prepared in phosphate-buffered saline (pH 7.4) through free radical polymerization of N-isopropylacrylamide (NIPAAm) monomer and a dextran macromer containing multiple hydrolytically degradable oligolactate-2-hydroxyethyl methacrylate units (Dex-lactateHEMA). Swelling measurement results demonstrated that four gels with feeding weight ratios of NIPAAm:Dex-lactateHEMA = 7:2, 6:3, 5:4, and 4:5 (w/w) were thermoresponsive by showing a lower critical solution temperature at approximately 32 degrees C. The swelling and degradation of the hydrogels strongly depended on temperature and hydrogel composition. An empirical mathematical model was established to describe the fast water absorption at the early stage and deswelling at the late stage of the hydrogels at 37 degrees C. Two hydrophilic model drugs, methylene blue and bovine serum albumin, were loaded into the hydrogels during the synthesis process. The molecular size of the drugs, the hydrophilicity and degradation of the hydrogels, and temperature played important roles in controlling the drug release.

摘要

开发了一系列具有热响应性和完全可生物降解特性的水凝胶,用于亲水性药物的水性包封和随温度变化的控释。通过N-异丙基丙烯酰胺(NIPAAm)单体和含有多个可水解降解的低聚乳酸-甲基丙烯酸2-羟乙酯单元的葡聚糖大分子单体(Dex-乳酸HEMA)的自由基聚合,在磷酸盐缓冲盐水(pH 7.4)中制备水凝胶。溶胀测量结果表明,NIPAAm:Dex-乳酸HEMA进料重量比为7:2、6:3、5:4和4:5(w/w)的四种凝胶具有热响应性,在约32℃时显示出较低的临界溶液温度。水凝胶的溶胀和降解强烈依赖于温度和水凝胶组成。建立了一个经验数学模型来描述水凝胶在37℃下早期的快速吸水和后期的去溶胀过程。在合成过程中,将两种亲水性模型药物亚甲蓝和牛血清白蛋白负载到水凝胶中。药物的分子大小、水凝胶的亲水性和降解以及温度在控制药物释放中起着重要作用。

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