β-环糊精星形聚合物负载苯丁酸氮芥性能

doi:10.7503/cjcu20180124

高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (10): 2350.doi: 10.7503/cjcu20180124

• 高分子化学 • 上一篇

β-环糊精星形聚合物负载苯丁酸氮芥性能

陈涛(), 黄婵

华东理工大学材料科学与工程学院, 上海市先进聚合物材料重点实验室, 上海 200237

收稿日期:2018-02-09 出版日期:2018-09-29 发布日期:2018-09-29
作者简介:
联系人简介: 陈涛, 男, 博士, 副教授, 主要从事高分子自组装及生物医用高分子研究. E-mail: tchen@ecust.edu.cn
基金资助:
国家重点研发计划项目(批准号: 2017YFB0309301, 2017YFB0309302)和上海市自然科学基金(批准号: 17ZR1407200)资助.

β-Cyclodextrin Based Star-like Polymer for Loading Chlorambucil^†

CHEN Tao^*(), HUANG Chan

Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering,East China University of Science and Technology, Shanghai 200237, China

Received:2018-02-09 Online:2018-09-29 Published:2018-09-29
Contact: CHEN Tao E-mail:tchen@ecust.edu.cn
Supported by:
† Supported by the National Key Research and Development Program of China(Nos. 2017YFB0309301, 2017YFB0309302) and the Natural Science Foundation of Shanghai, China(No. 17ZR1407200).

摘要/Abstract

摘要：

通过原子转移自由基聚合, 以溴化改性β-环糊精为引发剂, 合成了星形聚合物β-环糊精-聚甲基丙烯酸N,N-二甲氨基乙酯(β-CD-PDMAEMA). 采用红外光谱和核磁共振氢谱确定了星形聚合物的结构. 分别在乙醇和水介质中, 以β-CD-PDMAEMA为载体负载抗癌药物苯丁酸氮芥(CLB). 通过紫外吸收光谱分析比较了2种介质中β-CD-PDMAEMA对CLB的载药效率及在37 ℃、不同pH值下的体外释药性能, 分析了释药机理. 结果表明, 与乙醇相比, 以水为介质时CLB能更多地通过主客体作用进入星形聚合物内核β-CD的疏水空腔, 从而有更高的载药率, 药物突释期短、突释量少, 具有持续、高效的释放性能. CLB的释放属于扩散控制机理, PDMAEMA臂的质子化程度影响释药速率和累积释药量, 表现出明显的pH响应性, 酸性环境更有利于CLB的释放.

关键词: 聚甲基丙烯酸N, N-二甲氨基乙酯, β-环糊精;, 苯丁酸氮芥, 主客体相互作用

Abstract:

Star-like polymer with β-cyclodextrin core(β-CD) and poly(N,N-dimethylaminoethyl methacrylate) arms(PDMAEMA), β-CD-PDMAEMA, was synthesized by atom transfer radical polymerization using brominated β-CD as initiator. The structure of the polymer was determined by Fourier transform infrared spectrophotometer(FTIR) and ¹H nuclear magnetie resonance(NMR). The polymer was used to load hydrophobic anticancer drug chlorambucil(CLB) in both ethanol and water. The loading efficiency of CLB and in vitro release performance and mechanism at 37 ℃ in buffer solutions with various pH values were investigated by UV absorption spectroscopy. The results show that, compared to that in ethanol, the hydrophobic internal cavity of β-CD in the core of the star-like polymer includes more CLB in water, which leads to higher drug loading ratio, shorter and less burst release. The release of CLB from the star-like polymer follows the diffusion mechanism. The release rate and cumulative release amount of CLB are affected by the protonation degree of PDMAEMA arms, which results to pH responsive release behavior. The acidic condition is beneficial to more efficient and sustained release of CLB.

Key words: Poly(N, N-dimethylaminoethyl methacrylate), β-Cyclodextrin;, Chlorambucil, Host-guest interaction

中图分类号:

O631.1⁺1

TrendMD:

陈涛, 黄婵. β-环糊精星形聚合物负载苯丁酸氮芥性能. 高等学校化学学报, 2018, 39(10): 2350.

CHEN Tao,HUANG Chan. β-Cyclodextrin Based Star-like Polymer for Loading Chlorambucil^†. Chem. J. Chinese Universities, 2018, 39(10): 2350.

图/表 9

Scheme 1 Synthetic routes of star-like copolymer β-CD-PDMAEMA

Fig.1 FTIR spectra of β-CD(a), β-CD-Br(b) and β-CD-PDMAEMA(c)

Fig.2 1H NMR spectra of β-CD-Br(a) and β-CD-PDMAEMA(b) in CDCl3

Fig.3 GPC elution trace of β-CD-PDMAEMA in DMF

Fig.4 1H NMR spectra of CLB(a), β-CD-PDMAEMA(b) and β-CD-PDMAEMA/ CLB(c) in CD3OD

Fig.5 UV-Vis spectra of phenolphthalein in pH=9.4 buffer solutions of β-CD-PDMAEMA without(A) and with CLB(B)Concentration of β-CD-PDMAEMA/(mg·mL-1): a. 0.5; b. 1.0; c. 1.5; d. 2.0.

Fig.6 Release profiles of CLB from β-CD-PDMAEMA/CLB-1(A) and β-CD-PDMAEMA/CLB-2(B) in different buffer solutions at 37 ℃

Fig.7 Plots of lg(Mt/M∞) against lgt for CLB release from the β-CD-PDMAEMA/CLB-1(A) and β-CD-PDMAEMA/CLB-2(B) in different buffer solutions at 37 °Ca. pH=5.5; b. pH=7.4; c. pH=9.4.

Table 1 Release exponent(n), rate constant(lgk), and correlation coefficient(R2) for β-CD-PDMAEMA/CLB complexes

pH	β-CD-PDMAEMA/CLB-1			β-CD-PDMAEMA/CLB-2
pH	n	lgk	R²	n	lgk	R²
5.5	0.21	1.43	0.981	0.37	1.21	0.972
7.4	0.19	1.48	0.988	0.27	1.22	0.998
9.4	0.23	1.36	0.985	0.27	1.13	0.992

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β-环糊精星形聚合物负载苯丁酸氮芥性能

β-Cyclodextrin Based Star-like Polymer for Loading Chlorambucil^†

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β-环糊精星形聚合物负载苯丁酸氮芥性能

β-Cyclodextrin Based Star-like Polymer for Loading Chlorambucil†

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β-Cyclodextrin Based Star-like Polymer for Loading Chlorambucil^†