Thermosensitive polymers: synthesis, characterization, and delivery of proteins.
Thermosensitive polymers: synthesis, characterization, and delivery of proteins.
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DOI：
10.1016/j.ijpharm.2007.03.054
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发表时间：
2007-08
影响因子：
5.8
通讯作者：
Somnath Singh;D. Webster;Jagdish Singh
中科院分区：
文献类型：
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作者：
Somnath Singh;D. Webster;Jagdish Singh
合成了三种基于聚丙交酯或聚丙交酯-乙交酯与聚乙二醇或聚氧乙烷嵌段的三嵌段共聚物，并对其进行了表征。用凝胶渗透色谱和质子核磁共振波谱分别测定了重均相对分子质量和数均相对分子质量。用傅里叶变换红外光谱确定聚合物合成的完成度。用倒管法测定了热可逆的溶胶-凝胶转变温度和浓度。制备了两种不同聚合物浓度(20-30%，w/v)的溶菌酶或菠萝酶含量为5%(w/v)的合成聚合物，并对其体外释放进行了研究。采用四甲基偶氮唑盐(3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)比色法测定其体外生物相容性。用酶活测定法测定了溶菌酶和菠萝酶的生物活性。临界凝胶浓度在20-30%(w/v)范围内。体外生物相容性研究表明，各制剂均具有良好的生物相容性。随着聚合物浓度的增加，蛋白质的突释减少，蛋白质的体外释放延长。此外，释放样品中的溶菌酶和菠萝酶的生物活性显著高于对照样品(p<；0.05)。因此，上述温敏聚合物能够以受控的速度传递生物活性形式的蛋白质2-8周。
Three triblock copolymers based on the poly(lactide) or poly(lactide-co-glycolide) and poly(ethylene glycol) or poly(ethylene oxide) blocks were synthesized and characterized. The weight average molecular weight and number average molecular weight were determined by gel permeation chromatography and proton nuclear magnetic resonance spectroscopy, respectively. Fourier transform infrared spectroscopy was used to determine the completion of synthesis of polymers. Thermoreversible sol–gel transition temperature and concentration were determined by an inverted tube method. Two formulations each of three synthesized polymers containing 5% (w/v) of lysozyme or bromelain but differing in polymer concentrations (20–30%, w/v) were prepared and studied for in vitro release of the incorporated protein. In vitro biocompatibility of the delivery systems was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay. Biological activities of lysozyme and bromelain were determined by enzyme activity assays. Critical gelling concentrations were found in the range of 20–30% (w/v). In vitro biocompatibility study showed that all the formulations were biocompatible. Increasing the polymer concentration led to a decrease in burst release and extended the in vitro release of proteins. Furthermore, biological activities of lysozyme and bromelain in released samples were found to be significantly (p<0.05) greater in comparison to the control. Thus, the above thermosensitive polymers were able to deliver proteins in biologically active forms at a controlled rate for 2–8 weeks.