Najafizadeh Parvaneh, Ebrahimi Soltan Ahmad, Panjehshahin Mohammad Reza, Rezayat Sorkhabadi Seyed Mahdi
Department of Pharmacology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran;
Department of Pharmacology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran;
Iran J Med Sci. 2014 Nov;39(6):552-8.
Molecular imprinting is a method for synthesizing polymers with structure-selective adsorption properties with applications such as, selectivity binding, drug delivery systems and anti-bodies. The present study aims at optimizing the preparation of molecularly imprinted polymer (MIP) against l-phenylalanine, in order to increase phenylalanine-binding in Enzymatic Intestinal Simulated Fluid (ESIF).
The MIP for l-phenylalanine, as a water-soluble template, was successfully synthesized without derivatization. Synthesization was done by a UV polymerization method in which methacrylic acid (MAA), as a functional monomer, and ethylene glycol dimethacrylate (EGDMA), as a cross-linker, were used in the presence of five different porogenic solvents including; acetonitrile, tetrahydrofuran (THF), chloroform, toluene and dimethyl sulfoxide (DMSO). The selectivity of the MIP was examined using 19 different amino acids in human serum and was evaluated by HPLC. In addition, morphological studies were conducted using SEM.
The results showed that the obtained MIP with acetonitrile had the highest capacity and selectivity compared with other solvents. The data indicated that Phe-binding to MIP was significantly more than the former binding to NIP in EISF (P≤0.05). Moreover, in comparison with NIP and control group, MIP showed a better selectivity and binding for Phe. This could be used for the reduction of Phe in human serum samples of Phenylketonuria.
Our findings suggest that the MIP against Phe prepared with acetonitrile, showed a good selectivity and binding, which caused a reduction of blood Phe concentration in enzymatic simulated intestinal fluid and human serum sample of Phenylketonuria.
分子印迹是一种合成具有结构选择性吸附特性聚合物的方法,其应用包括选择性结合、药物递送系统和抗体等。本研究旨在优化针对L-苯丙氨酸的分子印迹聚合物(MIP)的制备,以提高其在酶促肠道模拟液(ESIF)中对苯丙氨酸的结合能力。
成功合成了以水溶性L-苯丙氨酸为模板的MIP,无需衍生化。通过紫外光聚合方法进行合成,其中使用甲基丙烯酸(MAA)作为功能单体,乙二醇二甲基丙烯酸酯(EGDMA)作为交联剂,同时存在五种不同的致孔溶剂,包括乙腈、四氢呋喃(THF)、氯仿、甲苯和二甲基亚砜(DMSO)。使用人血清中的19种不同氨基酸检测MIP的选择性,并通过高效液相色谱法进行评估。此外,使用扫描电子显微镜进行形态学研究。
结果表明,与其他溶剂相比,使用乙腈制备的MIP具有最高的容量和选择性。数据表明,在酶促肠道模拟液中,苯丙氨酸与MIP的结合明显多于其与非印迹聚合物(NIP)的结合(P≤0.05)。此外,与NIP和对照组相比,MIP对苯丙氨酸表现出更好的选择性和结合能力。这可用于降低苯丙酮尿症患者人血清样本中的苯丙氨酸水平。
我们的研究结果表明,用乙腈制备的针对苯丙氨酸的MIP表现出良好的选择性和结合能力,可降低酶促模拟肠液和苯丙酮尿症患者人血清样本中的血液苯丙氨酸浓度。