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

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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 m with narrow size distributions and similar zeta potentials. Free ara-C (F-ara-C) was rapidly eliminated from the circulation (t1/2= 1.43 h), whereas both conventional liposomes and gelliposomes showed prolonged elimination after intravenous injection with t1/2 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.
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Keywords: BIODISTRIBUTION; CYTARABINE; GELLIPOSOMES; PHARMACOKINETICS; THERMOSENSITIVE IN SITU GEL

Document Type: Research Article

Publication date: December 1, 2010

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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