期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 370, 期 1-2, 页码 210-215出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2008.11.028
关键词
Reverse thermo-responsive polymers; Micelles; Hydroxycamptothecin; Pharmacokinetics; Tissue distribution
资金
- Natural Science Funds from administration of Science and Technology of Shandong Province, China [Y2005C65]
New reverse thermo-responsive polymers, poly(ethylene oxide)-poly(propylene oxide) multi-block copolymers (poly(ether-carbonate)s) were synthesized. The micelles made of new reverse thermo-responsive polymers were also prepared loaded with the poorly soluble anticancer drug, hydroxycamptothecin (HCPT). The structure characterization of poly(ether-carbonate)s was determined by I H NMR and FT-IR analysis. The critical micelle concentration (CMC), critical micelle temperature (CMT), size distribution and drug release in vitro were determined. The pharmacokinetics and tissue distribution in vivo for novel copolymer micelles were studied. The experimental results showed that the micelles was spherical in appearance and dispersed well. The process of HCPT release from micelles in vitro was composed of two steps, abrupt release and sustained release. After i.v. administration (2 h), the drug concentration of poly(ether-carbonate) micelles group in liver in mice was 3.46 mu g/g, while that of HCPT injection group was 0.401 mu g/g. Compared with HCPT injection, the elimination half-life of poly(ether-carbonate) micelles group was prolonged remarkably from 1.3 to 12.5 h. The poly(ether-carbonate) micelles showed a combination of liver targeting and sustained drug release in experiments on animals. (C) 2008 Elsevier B.V. All rights reserved.
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