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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.

The potential of using CE frontal analysis (CE-FA) to study the interactions between a range of charged low molecular weight drug substances and liposomes was evaluated. The liposomes used were net negatively charged and consisted of 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphate monosodium salt in a ratio of 80/20 mol%. Apparent distribution coefficients (D(mem)), defined as the molar concentration of drug substance in the membrane phase divided by the molar concentration of drug substance in the aqueous phase, were successfully determined for six positively and eight negatively charged drug substances with log D(mem) ranging from 1.35 to 3.63. The extent of liposome-buffer distribution was found to be dependent on the drug concentration. The results obtained with the developed CE-FA method were in good agreement with results obtained by equilibrium dialysis. Furthermore, the CE-FA method was faster, less labor intensive and required smaller sample volumes (approximately 50 microL) compared with equilibrium dialysis. Thus, CE-FA is an efficient and useful tool for the characterization of interactions between liposomes and low molecular weight drug substances.

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Liposomes have attracted intensive attention as drug delivery systems in anti-cancer therapy. Since liposomes are constructed by self-assembling of phospholipids, ICP-MS is a suitable method for simultaneous determination of liposomes and encapsulated metallic drug substances such as platinumbased drugs. An efficient method for simultaneous determination of phosphorus and platinum in liposome samples has been established based on the use of xenon as a collision gas in DRC-ICP-MS. Under the optimum conditions with respect to signal to noise ratio, the interferences were suppressed and the detection limits of phosphorus and platinum were 0.3 and 0.05 ng mL À1 , respectively. Quality control was performed by using a certified reference material BCR 273 and biological reference materials. For the purpose of investigation of liposome stability and metallo-drug release from liposomes, a hyphenated method based on size exclusion chromatography was developed for separation of free and encapsulated platinum in a model liposome formulation of oxaliplatin. Moreover, an accelerated drug release study was performed by sonication of liposomal samples and using the developed hyphenated method to determine the drug leakage. It has been demonstrated that the SEC-DRC-ICP MS method was an efficient tool in the development and characterization of liposome based formulations of metallic drugs.