嵌段共聚物聚(异丙基丙烯酰胺)-b-聚(双丙酮丙烯酰胺)制备及其对叶酸的载负和释放

doi:10.3724/SP.J.1095.2014.30381

摘要/Abstract

摘要： 以N-异丙基丙烯酰胺(NIPAm)和双丙酮丙烯酰胺(DAAM)为原料，采用可逆加成断裂链转移(RAFT)可控聚合反应法合成了两亲性两嵌段共聚物聚(异丙基丙烯酰胺)-b-聚(双丙酮丙烯酰胺)(PNIPAm-b-PDAAM)，用红外光谱(FT-IR)、核磁共振(1H NMR)和凝胶渗透色谱(GPC)对其结构和组成进行了表征。这种共聚物在水溶液中能够自组装成稳定的聚合物胶束，通过荧光探针测得其低临界胶束浓度(CMC)约为7.0 mg/L。采用扫描电子显微镜(SEM)和动态激光光散射(DLS)测得，PNIPAm-b-PDAAM在水溶液中自组装成核壳结构的球形胶束，SEM测得其直径约150 nm，且分散性良好。以其聚合物胶束为载体、叶酸(FA)为模型药物，模拟人体生理环境进行药物体外释放。结果表明，叶酸的负载量及负载率分别为25%和74%。在人体温度37℃、pH值分别为4.0、6.86、9.18磷酸缓冲溶液(PBS)中，FA在20 h内的释放均比25 ℃快，释放速率随pH值增加而增大，最大累积释放率分别为31%、67%和72%。

关键词: 两亲性嵌段共聚物, 可逆加成-断裂链转移, 温敏性, 药物控制释放

Abstract: Amphiphilic diblock copolymer poly(N-isopropylacrylamide)-b-poly(diacetone acrylamide)(PNIPAM-b-PDAAM), which composed of N-isopropylacrylamide and diacetone acrylamide, was synthesized by reversible addition-fragmentation chain transfer(RAFT) polymerization. Its structure and composition were confirmed by FTIR spectroscopy, 1H nuclear magnetic resonance spectroscopy(1H NMR) and gel permeation chromatography(GPC). This copolymer can self-assemble into stable polymeric micelles. The critical micelle concentration values of the self-assembled micelles are about 7.0 mg/L in distilled water relying on fluorescent probe technique. The results measured by dynamic light scattering(DLS) and scanning electron microscopy(SEM) show that the self- assembled PNIPAM-b-PDAAM micelles exhibit spherical core-shell structure with well-defined dispersancy. The mean diameter of micelles estimated by SEM is around 150 nm. The model drug folic acid(FA) was loaded into the micelles as drug carrier material and the in vitro drug release behavior was investigated at body temperature. The results show that the FA-loaded content and the entrapment efficiency reach up to 25% and 72%，respectively. Compared with those at 25 ℃, in vitro release rates of FA from polymeric micelles in phosphate buffer solution(PBS) at temperatures 37 ℃，and different pH 4.0, 6.86 and 9.18， are all relatively faster within 20 h，and increase with increasing pH value and the largest accumulation release percentage is 31%， 67% and 72%， respectively.

Key words: amphiphilic block copolymer, reversible addition-fragmentation chain transfer, thermosensitivity, folic acid controlled release

中图分类号:

O632.6

齐印, 袁金芳, 高青雨. 嵌段共聚物聚(异丙基丙烯酰胺)-b-聚(双丙酮丙烯酰胺)制备及其对叶酸的载负和释放[J]. 应用化学, DOI: 10.3724/SP.J.1095.2014.30381.

QI Yin, YUAN Jinfang,GAO Qingyu*. Preparation of a Block Copolymer Poly(N-isopropylacrylamide)-b-poly(diacetone acrylamide) and Its Loading and Release Properties to Folic Acid[J]. Chinese Journal of Applied Chemistry, DOI: 10.3724/SP.J.1095.2014.30381.

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