title: Prednisolone retention in integrated liposomes by chemical approach and pharmaceutical approach.
abstract: The purpose of this study is to demonstrate a stable retention of prednisolone (PLS) in the unique liposomes integrated by lipophilic derivative approach and PEGylation approach. Palmitoyl prednisolone (Pal-PLS) was newly synthesized and used as a lipophilic derivative. The liposomes were composed of egg phosphatidylcholine (EggPC)/cholesterol (Chol) and L-alpha-distearoylphosphatidylcholine (DSPC)/Chol with or without L-alpha-distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG 2000) or -PEG 5000 (DSPE-PEG 5000). The retentions of PLS and Pal-PLS in the various liposomes were examined by ultrafiltration and gel filtration. Although PLS showed high trapping efficiency by all liposomes after ultrafiltration, low incorporation efficiency was observed in gel filtration. It indicates that PLS was released from the liposomes by a dilution with elution medium in gel filtration. Pal-PLS showed high incorporation into all liposomes after both ultrafiltration and gel filtration. The high incorporation of Pal-PLS into EggPC/Chol liposomes, however, was reduced by incubation with rat plasma in gel filtration. The reducing effect of rat plasma on drug incorporation into liposomes was inhibited by using DSPC and DSPE-PEGs. Thus, we systemically examined the drug retention in various liposomes and demonstrated the high retention of PLS in the liposomes integrated by lipophilic derivative approach and pharmaceutical approach using special lipids.
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Mugen
authors.initials: M
authors.lastname: Teshima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Koyo
authors.initials: K
authors.lastname: Nishida
authors.forename: Junzo
authors.initials: J
authors.lastname: Nakamura
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Terazono
authors.forename: Takashi
authors.initials: T
authors.lastname: Kitahara
authors.forename: Mikiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D002850:Chromatography, Gel; D016503:Drug Delivery Systems / Q000379:methods; D066298:In Vitro Techniques; D008081:Liposomes / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D014462:Ultrafiltration
chemical_list: D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C500349:palmitoyl prednisolone; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D011239:Prednisolone; C010942:1,2-distearoyllecithin