title: A novel liposome surface modification agent that prolongs blood circulation and retains surface ligand reactivity.
abstract: Liposomes are recognized as potentially useful drug carriers but many problems preclude practical medical application. Liposomes bind with serum proteins (opsonization) and are captured by the reticuloendothelial system cells in the liver and spleen, which limits their ability to deliver drugs to other target sites. Modification of lipids with flexible, hydrophilic polymers such as poly(ethylene glycol) (PEG) to yield sterically stabilized liposomes is one approach to improve liposome blood circulation and tissue distribution properties. In this study, we examined liposomes prepared using lipids modified with a new branched oligoglycerol (BGL) moiety for steric stabilization. This novel BGL comprised 14 glycerol units (termed BGL014) connected with flexible ether linkages, resulting in a branched cascade-like structure that is highly expanded in aqueous solution. BGL014 was coupled to 1,2-distearoylphosphatidylethanolamine to yield BGL014-modified lipids. Incorporation of BGL014 into liposomes (BGL014L) resulted in long blood circulation times, despite a much thinner fixed aqueous layer thickness compared to PEG formulations. BGL014 produced a liposome surface coating that appears to function through steric inhibition of non-specific protein binding without strong interference of specific protein-binding reactions. Liposome structure and functionality was maintained following BGL014-modification, as the incorporation ratio of drug remained high. These results suggest that the BGL014 modification of liposomes is a promising approach to produce stable and long circulating drug carriers capable of selective binding to specific proteins.
authors: a Drug Formulation Research and Development Laboratories, Production Division, Kyowa Hakko Kirin Co., Ltd. , 1188 Shimotogari, Nagaizumi-cho , Sunto-gun , Shizuoka , 411-8731 , Japan.
authors: Atsushi
authors: A
authors: Ishihara
authors: Masahiro
authors: M
authors: Yamauchi
authors: Tomoko
authors: T
authors: Tsuchiya
authors: Yukiteru
authors: Y
authors: Mimura
authors: Yutaka
authors: Y
authors: Tomoda
authors: Ayato
authors: A
authors: Katagiri
authors: Masaaki
authors: M
authors: Kamiya
authors: Hisao
authors: H
authors: Nemoto
authors: Toshiyuki
authors: T
authors: Suzawa
authors: Motoo
authors: M
authors: Yamasaki
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D001769:Blood / Q000378:metabolism; D002417:Cattle; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry; D005990:Glycerol / Q000031:analogs & derivatives* / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008422:Materials Testing; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012996:Solutions; D019809:Streptavidin / Q000737:chemistry; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; C000608077:BGL014; D004337:Drug Carriers; D008081:Liposomes; D011108:Polymers; D012996:Solutions; D014867:Water; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D019809:Streptavidin; D005990:Glycerol