Physicochemical characterization of a PEGylated liposomal drug formulation using capillary electrophoresis

被引:45
作者
Franzen, Ulrik [1 ]
Vermehren, Charlotte [2 ]
Jensen, Henrik [1 ]
Ostergaard, Jesper [1 ]
机构
[1] Univ Copenhagen, Dept Pharmaceut & Analyt Chem, Fac Pharmaceut Sci, DK-2100 Copenhagen, Denmark
[2] LiPlasome Pharma AS, Lyngby, Denmark
关键词
Affinity capillary electrophoresis; Electrokinetic chromatography; Frontal analysis; Oxaliplatin; PEGylated liposomes; TAYLOR DISPERSION ANALYSIS; DIFFUSION-COEFFICIENTS; CHROMATOGRAPHY; PHOSPHOLIPIDS; PARTICLES; COATINGS; BINDING; SOLUTE;
D O I
10.1002/elps.201000552
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:738 / 748
页数:11
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