TY - JOUR
T1 - Physicochemical characterization of a PEGylated liposomal drug formulation using capillary electrophoresis
AU - Franzen, Ulrik
AU - Vermehren, Charlotte
AU - Jensen, Henrik
AU - Østergaard, Jesper
N1 - Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
PY - 2011/3
Y1 - 2011/3
N2 - 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.
AB - 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.
KW - Antineoplastic Agents/chemistry
KW - Chemical Phenomena
KW - Chemistry, Pharmaceutical/methods
KW - Chromatography, Micellar Electrokinetic Capillary
KW - Electrophoresis, Capillary/methods
KW - Liposomes/chemistry
KW - Microscopy, Electron, Transmission
KW - Organoplatinum Compounds/chemistry
KW - Oxaliplatin
KW - Particle Size
KW - Polyethylene Glycols/chemistry
KW - Propranolol
U2 - 10.1002/elps.201000552
DO - 10.1002/elps.201000552
M3 - Journal article
C2 - 21365657
VL - 32
SP - 738
EP - 748
JO - Electrophoresis
JF - Electrophoresis
SN - 0173-0835
IS - 6-7
ER -