不同相对分子质量PEG-CHMC修饰乳剂对二次注射PE2000诱导产生ABC现象的研究

发布时间：2017-12-28 21:37

本文关键词：不同相对分子质量PEG-CHMC修饰乳剂对二次注射PE2000诱导产生ABC现象的研究　出处：《中国药剂学杂志(网络版)》2016年06期 　论文类型：期刊论文

【摘要】：目的研究比较不同相对分子质量PEG-CHMC修饰乳剂(PEG-CHMC coating emulsion,CHMCE)在大鼠体内的药动学行为及其对二次注射PEG2000-DSPE修饰乳剂(PEG2000-DSPE coating emulsion,PE2000)诱导的ABC现象,探究PEG相对分子质量对乳剂药动学行为及ABC现象的影响。方法以摩尔分数10%PEG修饰密度制备载药乳剂CHMCE和PE,以磷脂剂量5μmol·kg~(-1)进行大鼠尾静脉注射,分别于不同时间点进行静脉取血,处死大鼠后分离肝、脾组织,血浆和组织样品经处理后通过HPLC分析药物含量。结果通过比较药动学参数AUC(0-240 min)、tMRT(0-240 min)可知,高相对分子质量CHMCE(1 000、2 000、5 000)的循环时间较低相对分子质量CHMCE(400、600、800)有所延长,但延长程度不高;CHMCE诱导PE2000产生ABC现象的结果显示,低相对分子质量CHMCE无ABC现象,而高相对分子质量CHMCE诱导了一定强度的ABC现象(CHMCE1000、CHMCE2000和CHMCE5000的ABC index(0-60 min)分别为0.64、0.59和0.53)。结论 PEG相对分子质量在CHMCE的药动学行为及ABC现象的产生中具有重要影响,研究结果对PEG相对分子质量在ABC现象中的影响规律进行了补充,为PEG化制剂相对分子质量的选择提供了一定借鉴。
[Abstract]:Objective to compare the relative molecular mass of PEG-CHMC modified emulsion (PEG-CHMC coating emulsion, different CHMCE) in rats in vivo pharmacokinetic behavior of two injections of PEG2000-DSPE modified emulsion (PEG2000-DSPE coating emulsion, PE2000) ABC phenomenon induced, explore the impact of the molecular weight of PEG on the pharmacokinetics of emulsion and ABC phenomenon. Methods the mole fraction of 10%PEG modified density of prepared drug loaded emulsion CHMCE and PE, with the dose of 5 u mol kg~ phospholipid (-1) rats by tail vein injection, respectively. Venous blood at different time points, the separation of the liver and spleen tissues of rats, plasma and tissue samples were processed by HPLC analysis of drug content. Results by comparing the pharmacokinetic parameters of AUC (0-240 min), tMRT (0-240 min) showed that the high molecular weight of CHMCE (1000, 2000, 5000) the cycle time of low molecular weight CHMCE (400, 600, 800) has been extended, but the extension degree is not high; the CHMCE induced PE2000 production ABC phenomenon the results showed that low molecular weight CHMCE ABC ABC phenomenon, and the phenomenon of high molecular weight CHMCE was induced by a certain intensity (CHMCE1000, CHMCE2000 and CHMCE5000 ABC index (0-60 min) were 0.64, 0.59 and 0.53). Conclusion the relative molecular mass of PEG has an important influence on the pharmacokinetic behavior and the occurrence of ABC phenomenon in CHMCE. The research results complement the influence rule of PEG relative molecular mass in the ABC phenomenon, providing a reference for the selection of relative molecular mass of PEG formulation.
【作者单位】：沈阳药科大学药学院;
【基金】：国家自然科学基金资助项目(81072602)
【分类号】：R943
【正文快照】： 间;ABC index近些年,使用聚乙二醇(polyethylene glycol,PEG)对纳米载药体系进行修饰,即PEG化(pegylation)技术,极大地解决了载体易与血浆中调理素结合而被单核巨噬细胞系统(mononuclearphagocytic system,MPS)摄取这一应用障碍,延长载体在血液中的循环时间、提高载体的靶向性

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