文章基本信息

标题：PEGylated Liposomes Loading Palmitoyl Prednisolone for Prolonged Blood Concentration of Prednisolone
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作者：Mugen Teshima ; Shigeru Kawakami ; Shintaro Fumoto 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2006
卷号：29
期号：7
页码：1436-1440
DOI：10.1248/bpb.29.1436
出版社：The Pharmaceutical Society of Japan
摘要：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 ( 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.
关键词：drug delivery system (DDS);prednisolone;liposome;lipophilic derivative;polyethylene glycol (PEG)