title: Physicochemical characterization of a PEGylated liposomal drug formulation using capillary electrophoresis.
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.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Franzen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Vermehren
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
authors.forename: Jesper
authors.initials: J
authors.lastname: Østergaard
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods; D020374:Chromatography, Micellar Electrokinetic Capillary; D019075:Electrophoresis, Capillary / Q000379:methods*; D008081:Liposomes / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D009944:Organoplatinum Compounds / Q000737:chemistry*; D000077150:Oxaliplatin; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011433:Propranolol
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011092:Polyethylene Glycols; D011433:Propranolol