Effects of Interior Gelation on Pharmacokinetics and Biodistribution of Liposomes Encapsulating an Anti-Cancer Drug Cytarabine

被引:10
|
作者
Zhang, Bei [1 ]
Lu, Yi [1 ]
Chen, Jian [1 ]
Wu, Wei [1 ]
机构
[1] Fudan Univ, Dept Pharmaceut, Sch Pharm, Shanghai 201203, Peoples R China
关键词
Pharmacokinetics; Biodistribution; Gelliposomes; Thermosensitive In Situ Gel; Cytarabine; CHITOSAN-BASED HYDROGEL; ANTI-TUMOR ACTIVITY; ARA-C; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; DELIVERY; LEUKEMIA; THERAPY; CIRCULATION; CANCER; CELLS;
D O I
10.1166/jbn.2010.1162
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Interior gelation of liposomes leads to changes in the physicochemical properties of liposomes, such as increased rigidity of the lipid bilayers, modified shape, improved physical stability and sustained release of a model drug cytarabine (ara-C), all of which may affect the performance of liposomes in vivo. In this study, we investigated the pharmacokinetics of liposomes with gelated interior (gelliposomes) in rats and the biodistribution in mice using conventional liposomes as control. The ara-C gelliposomes (GL-ara-C) and conventional liposomes (CL-ara-C) were prepared by a thin-film dispersion method. Both liposomes were determined to have a mean size of about 1.2 mu m with narrow size distributions and similar zeta potentials. Free ara-C (F-ara-C) was rapidly eliminated from the circulation (t(1/2) = 1.43 h), whereas both conventional liposomes and gelliposomes showed prolonged elimination after intravenous injection with t(1/2) of 5.88 h and 27.54 h, respectively. The AUC of CL-ara-C and GL-ara-C were 1.67 and 2.68 times greater than that of F-ara-C, respectively. Due to phagocytic uptake, the two liposomal formulations were mainly distributed in liver, spleen and kidney. Our data indicated that gelliposomes showed slower elimination and prolonged resident time in the body. Compared with that of conventional liposomes, the distribution of gelliposomes was increased in most of the tissues we investigated. These results indicated that interior gelation caused the changes in the physicochemical properties of liposomes, and these changes improved their performance in vivo.
引用
收藏
页码:704 / 709
页数:6
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