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由带有聚(N-异丙基丙烯酰胺)和甘氨酸乙酯作为侧基的两亲性聚磷腈自组装形成的热响应性聚合物胶束:聚合物合成、表征及体外药物释放研究

Thermally responsive polymeric micelles self-assembled by amphiphilic polyphosphazene with poly(N-isopropylacrylamide) and ethyl glycinate as side groups: polymer synthesis, characterization, and in vitro drug release study.

作者信息

Zhang Jian Xiang, Qiu Li Yan, Jin Yi, Zhu Kang Jie

机构信息

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310031, China.

出版信息

J Biomed Mater Res A. 2006 Mar 15;76(4):773-80. doi: 10.1002/jbm.a.30604.

Abstract

Thermally responsive amphiphilic poly(N-isopropylacrylamide) (PNIPAm)-grafted-polyphosphazene (PNIPAm-g-PPP) was synthesized by stepwise cosubstitution of chlorine atoms on polymer backbones with amino-terminated NIPAm oligomers and ethyl glycinate (GlyEt). Polymer structure was confirmed by FT-IR, (1)H NMR, elemental analysis, and GPC. The thermosensitivity of PNIPAm-g-PPP aqueous solution was investigated by turbidity method. The lower critical solution temperature (LCST) of PNIPAm-g-PPP was observed to be approximately 30 degrees C in water, while it was 24 degrees C in 0.1M PBS (pH 7.4). Micellization behavior of PNIPAm-g-PPP in aqueous solution was characterized by fluorescence probe technique, TEM, and DLS. The critical micelle concentration (CMC), thus, determined was 0.0187 g/L. Both TEM and DLS measurement suggested that the diameter of micelles was approximately 190 nm at 20 degrees C. Diflunisal (DIF)-loaded micelles were prepared by dialysis method. In vitro release test at various temperatures was also performed to study the effect of temperature on the drug release profiles. It was demonstrated that DIF release from PNIPAm-g-PPP micelles was slower at the temperature of 37 degrees C than that at 4 degrees C.

摘要

通过用氨基封端的N-异丙基丙烯酰胺(NIPAm)低聚物和甘氨酸乙酯(GlyEt)逐步共取代聚合物主链上的氯原子,合成了热响应性两亲性聚(N-异丙基丙烯酰胺)(PNIPAm)接枝聚磷腈(PNIPAm-g-PPP)。通过傅里叶变换红外光谱(FT-IR)、核磁共振氢谱(¹H NMR)、元素分析和凝胶渗透色谱(GPC)对聚合物结构进行了确认。采用浊度法研究了PNIPAm-g-PPP水溶液的热敏感性。观察到PNIPAm-g-PPP在水中的低临界溶液温度(LCST)约为30℃,而在0.1M磷酸盐缓冲液(PBS,pH 7.4)中为24℃。通过荧光探针技术、透射电子显微镜(TEM)和动态光散射(DLS)对PNIPAm-g-PPP在水溶液中的胶束化行为进行了表征。由此确定的临界胶束浓度(CMC)为0.0187 g/L。TEM和DLS测量均表明,在20℃时胶束直径约为190 nm。采用透析法制备了载双氯芬酸(DIF)的胶束。还进行了不同温度下的体外释放试验,以研究温度对药物释放曲线的影响。结果表明,DIF从PNIPAm-g-PPP胶束中的释放在37℃时比在4℃时慢。

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