title: Drug-liposome distribution phenomena studied by capillary electrophoresis-frontal analysis.
abstract: The potential of using CE frontal analysis (CE-FA) for the study of low-molecular-weight drug-liposome interactions was assessed. The interaction of bupivacaine, brompheniramine, chlorpromazine, imipramine, and ropivacaine with net negatively charged 80/20 mol% 1-oleoyl-2-palmitoyl-sn-glycero-3-phosphocholine/egg yolk phosphatidic acid liposome suspensions in HEPES buffer at pH 7.4 was investigated. The fraction of free drug as a function of lipid concentration was measured and apparent liposome-buffer distribution coefficients were determined for the basic drug substances. The distribution coefficients increased in the order ropivacaine, bupivacaine, brompheniramine, imipramine, and chlorpromazine. The developed CE method was relatively fast allowing estimates of drug-liposome affinity to be obtained within 15 min. CE-FA may have the potential to become a valuable tool for the characterization of drug-liposome interactions in relation to estimation of drug lipophilicity and for the evaluation of drug distribution in liposomal drug delivery systems.
authors.affiliation: Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Ostergaard
authors.forename: Lene
authors.initials: L
authors.lastname: Jorgensen
authors.forename: Anne
authors.initials: A
authors.lastname: Engelbrecht Thomsen
authors.forename: Susan
authors.initials: S
authors.lastname: Weng Larsen
authors.forename: Claus
authors.initials: C
authors.lastname: Larsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Jensen
mesh_terms: D016503:Drug Delivery Systems; D019075:Electrophoresis, Capillary / Q000379:methods; D008081:Liposomes / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*
chemical_list: D008081:Liposomes; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines