title: Release of drugs from liposomes varies with particle size.
abstract: The efficacy of many drugs is improved by liposomal formulations. The greatest improvements in therapeutic benefits are achieved if the drug is retained in the liposomes for several hours after administration. Many basic drugs can be concentrated efficiently into liposomes in response to a transmembrane pH gradient. However, the rate of release from liposomal formulations is drug-dependent; for example, doxorubicin is released slowly from liposomes whereas vincristine leaks out rapidly. The aim of this study was to identify the causes of the rapid release of drugs from liposomes and then to apply this knowledge to the development of more stable formulations. Our initial focus was to explore the influence of liposomal size on the rate of release of drugs. The retention of doxorubicin within liposomes was independent of the particle size as far as this experimental condition was concerned. However, the rate of release of vincristine varied in relation to the particle size of the liposomes; vincristine was retained more effectively in larger liposomes. Experimental data generated using (31)P-NMR analysis and trap volume measurements, indicated that the number of lipid bilayers in liposomes increased as the particle size was increased. Additional lipid bilayers are likely to present a more effective barrier thereby slowing the release of drugs.
authors.affiliation: Drug Formulation Research Laboratories, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co Ltd, Sunto-Gun, Shizuoka, Japan. masahiro.yamauchi@kyowa.co.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamauchi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Abe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Uosaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakakura
authors.forename: Noboru
authors.initials: N
authors.lastname: Aoki
mesh_terms: D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry; D053835:Unilamellar Liposomes / Q000737:chemistry*; D014750:Vincristine / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D008051:Lipid Bilayers; D004364:Pharmaceutical Preparations; D010713:Phosphatidylcholines; D053835:Unilamellar Liposomes; D014750:Vincristine; D004317:Doxorubicin