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用于固定化人工膜色谱的双链磷脂酰胆碱功能化聚合物整体柱的研制。

Development of double chain phosphatidylcholine functionalized polymeric monoliths for immobilized artificial membrane chromatography.

作者信息

Wang Qiqin, Peng Kun, Chen Weijia, Cao Zhen, Zhu Peijie, Zhao Yumei, Wang Yuqiang, Zhou Haibo, Jiang Zhengjin

机构信息

Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University, Guangzhou 510632, China.

Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University, Guangzhou 510632, China; School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China; School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510006, China.

出版信息

J Chromatogr A. 2017 Jan 6;1479:97-106. doi: 10.1016/j.chroma.2016.11.046. Epub 2016 Nov 24.

Abstract

This study described a simple synthetic methodology for preparing biomembrane mimicking monolithic column. The suggested approach not only simplifies the preparation procedure but also improves the stability of double chain phosphatidylcholine (PC) functionalized monolithic column. The physicochemical properties of the optimized monolithic column were characterized by scanning electron microscopy, energy-dispersive X-ray spectrometry, and nano-LC. Satisfactory column permeability, efficiency, stability and reproducibility were obtained on this double chain PC functionalized monolithic column. It is worth noting that the resulting polymeric monolith exhibits great potential as a useful alternative of commercial immobilized artificial membrane (IAM) columns for in vitro predication of drug-membrane interactions. Furthermore, the comparative study of both double chain and single chain PC functionalized monoliths indicates that the presence or absence of glycerol backbone and the number of acyl chains are not decisive for the predictive ability of IAM monoliths on drug-membrane interactions. This novel PC functionalized monolithic column also exhibited good selectivity for a protein mixture and a set of pharmaceutical compounds.

摘要

本研究描述了一种制备仿生物膜整体柱的简单合成方法。所建议的方法不仅简化了制备过程,还提高了双链磷脂酰胆碱(PC)功能化整体柱的稳定性。通过扫描电子显微镜、能量色散X射线光谱和纳米液相色谱对优化后的整体柱的物理化学性质进行了表征。在这种双链PC功能化整体柱上获得了令人满意的柱渗透性、效率、稳定性和重现性。值得注意的是,所得的聚合物整体柱作为商业固定化人工膜(IAM)柱的有用替代品,在体外预测药物-膜相互作用方面具有巨大潜力。此外,对双链和单链PC功能化整体柱的比较研究表明,甘油主链的有无以及酰基链的数量对于IAM整体柱对药物-膜相互作用的预测能力并非决定性因素。这种新型PC功能化整体柱对蛋白质混合物和一组药物化合物也表现出良好的选择性。

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