5-氟尿嘧啶分子表面印迹微球MIP-PSSS/CPVA的制备及其体外结肠定位释药特性研究

doi:10.6023/A12070402

摘要/Abstract

以对苯乙烯磺酸钠(SSS)为功能单体, 以N,N'-亚甲基双丙烯酰胺(MBA)为交联剂, 采用铈盐-羟基氧化还原引发体系, 在交联聚乙烯醇(CPVA)微球表面实施了5-氟尿嘧啶(5-FU)分子的表面印迹, 在微球CPVA表面形成印迹聚合物(MIP)层, 即制备了5-FU分子印迹微球MIP-PSSS/CPVA. 采用红外光谱(FTIR)和扫描电子显微镜(SEM)法, 对印迹微球进行了表征. 重点考察分析了印迹微球对5-氟尿嘧啶(5-FU)的结合(载药)性能与结合机理, 考察探索了载药微球在不同pH介质中的释放行为. 实验结果表明, 基于本体系特殊的羟基-铈盐表面引发体系, 可有效地实现5-FU分子的表面印迹, 在微球CPVA表面形成分布有大量5-FU分子印迹空穴的聚合物层. 在酸性介质中, 受强静电相互作用的驱动, 印迹微球MIP-PSSS/CPVA对5-FU分子表现出很强的结合能力, 结合容量达110 mg/g, 可实现有效载药. 载药微球的释药行为既具有强烈的pH依赖性, 又具有时滞性: 在模拟胃液中(pH＝1), 基本不释药; 在模拟小肠液中(pH＝6.8), 释药量很小; 在模拟结肠液中(pH＝7.4), 则发生突释, 表现出高效的结肠定位释放行为.

关键词: 表面印迹, 对苯乙烯磺酸钠, 交联聚乙烯醇微球, 5-氟尿嘧啶, 结肠定位释放

The aim of this work was to investigate the possibility to constitute a colon-specific drug delivery for 5-fluorouracil (5-FU) by using molecularly imprinted polymers (MIPs) in simulated gastrointestinal fluids, compared to non molecularly imprinted polymers (NMIPs). Surface imprinting of 5-FU was performed on crosslinked polyvinyl alcohol microspheres (CPVA microspheres) with sodium 4-styrene sulfonate (SSS) as functional monomer and with N,N'-methylene bisacrylamide (MBA) as crosslinker by using cerium salt-hydroxyl group redox initiation system, and 5-FU-imprinted microspheres MIP-PSSS/CPVA, on which there exists a layer of molecular imprinting, were obtained. The chemical structure and morphology of MIP-PSSS/CPVA microspheres were characterized with infrared spectrum (FTIR) and scanning electron microscope (SEM). The binding property of the imprinted microspheres MIP-PSSS/CPVA for 5-fluorouracil (5-FU), namely drug carrying ability, was mainly investigated and the binding mechanism was explored. The in vitro release behavior of the drug-carried microspheres was also examined. The experimental results show that based on the special cerium salt-hydroxyl group redox initiation system in this investigation, the surface imprinting of 5-FU can be effectively realized, and a polymer layer, in which a lot of 5-FU-imprinted caves are distributed, can be formed on the surfaces of CPVA microspheres. In the acidic medium, the imprinted microspheres MIP-PSSS/CPVA exhibit very strong binding ability for 5-FU by driving of electrostatic interaction. The binding capacity can get up to 105 mg/g, displaying the high efficiency of drug carrying. The in vitro release behavior of the drug carrying microspheres not only is highly pH-dependent, but also is time-delayed. The release of pH-dependent is owing to strong electrostatic action between 5-FU molecules and the sulfonate groups in the imprinted caves at low pH. Along with the increase of pH value of the medium, the weakening of the protonation degree of the amino groups of 5-FU, and the electrostatic interaction between MIP-PSSS/CPVA microspheres and 5-FU molecule decreases, leading to the enhancement of 5-FU release. The release of time-delayed coming from the restraining action of the MIP-PSSS/CPVA microspheres for 5-FU, and this binding action is the synergism of strong electrostatic action between 5-FU molecules and the sulfonate groups in the imprinted caves and the 5-FU molecule diffusion resistance caused by the imprinted caves. The experiment results show in the medium of pH＝1, the drug does not be released; in the simulated intestine fluid (pH＝6.8), the drug release is small; in the simulated colon fluid (pH＝7.4), the sudden delivery phenomenon will be produced, displaying an excellent colon-specific drug delivery behavior.

Key words: surface imprinting, sodium 4-styrene sulfonate, crosslinked polyvinyl alcohol microspheres, 5-fluorouracil, colon-specific drug delivery

引用此文

门吉英, 高保娇, 陈志萍, 么兰. 5-氟尿嘧啶分子表面印迹微球MIP-PSSS/CPVA的制备及其体外结肠定位释药特性研究[J]. 化学学报, 2012, 70(21): 2273-2280.

Men Jiying, Gao Baojiao, Chen Zhiping, Yao Lan. Preparation of 5-Fluorouracil-Surface Imprinted Microspheres MIP-PSSS/CPVA and Studies on Its Character of Colon-Specific Drug Delivery[J]. Acta Chimica Sinica, 2012, 70(21): 2273-2280.

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