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PEGylated Liposomes Loading Palmitoyl Prednisolone for Prolonged Blood Concentration of Prednisolone


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タイトル: PEGylated Liposomes Loading Palmitoyl Prednisolone for Prolonged Blood Concentration of Prednisolone
著者: Teshima, Mugen / Kawakami, Shigeru / Fumoto, Shintaro / Nishida, Koyo / Nakamura, Junzo / Nakashima, Mikiro / Nakagawa, Hiroo / Ichikawa, Nobuhiro / Sasaki, Hitoshi
発行日: 2006年 7月
出版者: Pharmaceutical Society of Japan
引用: Biological & Pharmaceutical Bulletin v.29(7) p.1436-1440, 2006
抄録: We investigated the pharmacokinetic behavior of palmitoyl prednisolone (Pal-PLS) and its liposomes with L-α-distearoylphosphatidylcholine (DSPC) and cholesterol (Chol) with or without L-α-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 (Kel) 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.
キーワード: drug delivery system (DDS) / prednisolone / liposome / lipophilic derivative / polyethylene glycol (PEG)
URI: http://hdl.handle.net/10069/8343
ISSN: 09186158
DOI: 10.1248/bpb.29.1436
PubMed ID: 16819184
関連リンク : http://dx.doi.org/10.1248/bpb.29.1436
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:130 学術雑誌論文

引用URI : http://hdl.handle.net/10069/8343

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