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采用毛细管电泳法对聚乙二醇化脂质体药物制剂进行理化特性分析。

Physicochemical characterization of a PEGylated liposomal drug formulation using capillary electrophoresis.

机构信息

Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Electrophoresis. 2011 Mar;32(6-7):738-48. doi: 10.1002/elps.201000552. Epub 2011 Mar 1.

Abstract

In this work, the applicability of using CE to perform a physicochemical characterization of a PEGylated liposomal drug formulation of the anti-cancer agent oxaliplatin was examined. Characterization of the liposomal drug formulation using CE instrumentation encompassed: determination of the electrophoretic mobilities, size determination by Taylor dispersion analysis and interaction studies. Electrophoretic mobilities determined by CE were compared with the results obtained by laser Doppler electrophoresis, which were found to be subject to larger variation. Average hydrodynamic diameters of the liposome preparations, as determined by Taylor dispersion analysis, were in the range of 61-84 nm and were compared with the results obtained by dynamic light scattering. Interactions between oxaliplatin (and paracetamol) and the PEGylated liposome were non-detectable by CE frontal analysis as well as by liposome electrokinetic chromatography. In contrast, for the more lipophilic compound propranolol, apparent liposome-aqueous phase distribution coefficients (D(lip) ) were successfully determined by both electrokinetic chromatography (log D(lip) =2.10) and by CE frontal analysis (log D(lip) =2.14). It is envisioned that CE and capillary-based techniques, including Taylor dispersion analysis, will be useful tools for the characterization of nanoparticulate (e.g. liposomal) drug formulations.

摘要

在这项工作中,考察了使用 CE 对 PEG 化脂质体药物制剂(奥沙利铂抗癌剂)进行物理化学特性分析的适用性。使用 CE 仪器对脂质体药物制剂进行的特性描述包括:电泳迁移率的测定、通过泰勒分散分析进行的粒径测定以及相互作用研究。CE 确定的电泳迁移率与激光多普勒电泳的结果进行了比较,发现后者的变化较大。通过泰勒分散分析确定的脂质体制剂的平均水动力直径在 61-84nm 范围内,并与动态光散射的结果进行了比较。CE 前沿分析和脂质体电动色谱均未检测到奥沙利铂(和扑热息痛)与 PEG 化脂质体之间的相互作用。相比之下,对于疏水性更高的化合物普萘洛尔,通过电动色谱(logDlip=2.10)和 CE 前沿分析(logDlip=2.14)成功地确定了其表观脂质体-水相间分配系数(Dlip)。可以预见,CE 和基于毛细管的技术,包括泰勒分散分析,将成为纳米颗粒(例如脂质体)药物制剂特性描述的有用工具。

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