title: PEGylated liposomes loading palmitoyl prednisolone for prolonged blood concentration of prednisolone.
abstract: We investigated the pharmacokinetic behavior of palmitoyl prednisolone (Pal-PLS) and its liposomes with L-alpha-distearoylphosphatidylcholine (DSPC) and cholesterol (Chol) with or without L-alpha-distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG 2000) after their intravenous administration in rats. Pal-PLS rapidly disappeared from the systemic circulation and prednisolone (PLS) was regenerated after the administration of DSPC/Chol liposomes. PEGylated liposomes including DSPE-PEG 2000, however, successfully maintained high blood concentrations of Pal-PLS and PLS. The blood profiles of drugs after the administration of liposomal Pal-PLS were analyzed according to a two-compartment model. The larger content of DSPE-PEG 2000 in DSPC/Chol liposomes showed a lower first order elimination rate constant from the central compartment (K(el)) and clearance (CL). The area under the concentration-time curve (AUC) of Pal-PLS and PLS in PEGylated liposomes was larger than DSPC/Chol liposomes. The mean resident time (MRT) of Pal-PLS and PLS was also prolonged by PEGylated liposomes. Although DSPC/Chol liposomes showed a high distribution of Pal-PLS in the liver and spleen, PEGylated liposomes significantly decreased the liver distribution of Pal-PLS. The biliary and urinary excretions of drugs for 240 min after drug administration were less than 1% of the administrated dose in any formulations. In conclusion, PEGylated liposomes, including Pal-PLS, are useful for maintain the PLS concentration in the blood after intravenous administration.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital of Medicine and Dentistry, Japan.
authors.forename: Mugen
authors.initials: M
authors.lastname: Teshima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fumoto
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
authors.forename: Mikiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Hiroo
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ichikawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D007700:Kinetics; D008081:Liposomes; D008297:Male; D011092:Polyethylene Glycols; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; C500349:palmitoyl prednisolone; D011092:Polyethylene Glycols; D011239:Prednisolone