title: Controlled release of a protein kinase inhibitor UCN-01 from liposomes influenced by the particle size.
abstract: A protein kinase inhibitor UCN-01 binds with high affinity to human alpha 1-acid glycoprotein (hAGP) which may compromise the drugs therapeutic effectiveness. Liposomal formulations of UCN-01 have been evaluated as a means of reducing the impact of binding to hAGP. However, in an initial study, UCN-01 was released rapidly from liposomes added to rat plasma containing hAGP. The purpose of this study was to develop a liposomal formulation of UCN-01 that only slowly released drug. Liposomes composed of lipids with a high phase transition temperature and having an average particle size of 120 nm and above reduced leaking of UCN-01 when the formulations were evaluated by adding to rat plasma containing hAGP. Furthermore, formulations composed of larger liposomes were also more effective in vivo; in tests in which liposomal preparations were injected together with hAGP into rats, more UCN-01 was retained in liposomes for 24h after administration of 155 nm liposomes as compared to 112 nm liposomes.
authors: Drug Formulation Research Laboratories, Pharmaceutical Research Center, Kyowa Hakko Kogyo Co. Ltd., 1188 Shimotogari, Nagaizumi-Cho, Sunto-Gun, Shizuoka 411-8731, Japan. Masahiro.yamauchi@kyowa.co.jp
authors: Masahiro
authors: M
authors: Yamauchi
authors: Hiroko
authors: H
authors: Kusano
authors: Etsuko
authors: E
authors: Saito
authors: Masayuki
authors: M
authors: Abe
authors: Kyoko
authors: K
authors: Tsutsumi
authors: Yoichi
authors: Y
authors: Uosaki
authors: Masashi
authors: M
authors: Nakakura
authors: Yasuki
authors: Y
authors: Kato
authors: Noboru
authors: N
authors: Aoki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D008081:Liposomes; D008297:Male; D009961:Orosomucoid / Q000378:metabolism; D010316:Particle Size; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D044366:Transition Temperature
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D008081:Liposomes; D009961:Orosomucoid; D047428:Protein Kinase Inhibitors; C054852:7-hydroxystaurosporine; D019311:Staurosporine