Zhang Wei, She Xuhui, Wang Liping, Fan Huajun, Zhou Qing, Huang Xiaowen, Tang James Z
School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou 510006, China.
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Materials (Basel). 2017 Apr 28;10(5):475. doi: 10.3390/ma10050475.
A novel molecular imprinting polymer (MIP) was prepared by bulk polymerization using sulpiride as the template molecule, itaconic acid (ITA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the crosslinker. The formation of the MIP was determined as the molar ratio of sulpiride-ITA-EGDMA of 1:4:15 by single-factor experiments. The MIP showed good adsorption property with imprinting factor of 5.36 and maximum adsorption capacity of 61.13 μmol/g, and was characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR) and surface area analysis. With the structural analogs (amisulpride, tiapride, lidocaine and cisapride) and small molecules containing a mono-functional group (p-toluenesulfonamide, formamide and 1-methylpyrrolidine) as substrates, static adsorption, kinetic adsorption, and rebinding experiments were also performed to investigate the selective adsorption ability, kinetic characteristic, and recognition mechanism of the MIP. A serial study suggested that the highly selective recognition ability of the MIP mainly depended on binding sites provided by N-functional groups of amide and amine. Moreover, the MIP as solid-phase extractant was successfully applied to extraction of sulpiride from the mixed solution (consisted of p-toluenesulfonamide, sulfamethoxazole, sulfanilamide, p-nitroaniline, acetanilide and trimethoprim) and serum sample, and extraction recoveries ranged from 81.57% to 86.63%. The tentative tests of drug release in stimulated intestinal fluid (pH 6.8) demonstrated that the tablet with the MIP-sulpiride could obviously inhibit sulpiride release rate. Thus, ITA-based MIP is an efficient and promising alternative to solid-phase adsorbent for extraction of sulpiride and removal of interferences in biosample analysis, and could be used as a potential carrier for controlled drug release.
以舒必利为模板分子、衣康酸（ITA）为功能单体、乙二醇二甲基丙烯酸酯（EGDMA）为交联剂，通过本体聚合法制备了一种新型分子印迹聚合物（MIP）。通过单因素实验确定MIP的形成条件为舒必利-ITA-EGDMA的摩尔比为1:4:15。该MIP表现出良好的吸附性能，印迹因子为5.36，最大吸附容量为61.13 μmol/g，并通过扫描电子显微镜（SEM）、傅里叶变换红外光谱（FT-IR）和表面积分析对其进行了表征。以结构类似物（氨磺必利、硫必利、利多卡因和西沙必利）和含单官能团的小分子（对甲苯磺酰胺、甲酰胺和1-甲基吡咯烷）为底物，进行了静态吸附、动力学吸附和再结合实验，以研究MIP的选择性吸附能力、动力学特征和识别机制。一系列研究表明，MIP的高选择性识别能力主要取决于酰胺和胺的N-官能团提供的结合位点。此外，该MIP作为固相萃取剂成功应用于从混合溶液（由对甲苯磺酰胺、磺胺甲恶唑、磺胺、对硝基苯胺、乙酰苯胺和甲氧苄啶组成）和血清样品中萃取舒必利，萃取回收率在81.57%至86.63%之间。在模拟肠液（pH 6.8）中的药物释放初步试验表明，含MIP-舒必利的片剂可明显抑制舒必利的释放速率。因此，基于ITA的MIP是一种高效且有前景的固相吸附剂替代品，可用于舒必利的萃取和生物样品分析中的干扰去除，并可作为药物控释的潜在载体。
