Preparation, pharmacokinetics and tissue distribution of micelles made of reverse thermo-responsive polymers.
New reverse thermo-responsive polymers, poly(ethylene oxide)-poly(propylene oxide) multiblock 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 (1)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 (2h), the drug concentration of poly(ether-carbonate) micelles group in liver in mice was 3.46microg/g, while that of HCPT injection group was 0.401microg/g. Compared with HCPT injection, the elimination half-life of poly(ether-carbonate) micelles group was prolonged remarkably from 1.3 to 12.5h. The poly(ether-carbonate) micelles showed a combination of liver targeting and sustained drug release in experiments on animals.
Yang
Xingguo
X
Department of Pharmaceutics, School of Pharmacy, Shandong University, 44 Wenhuaxi Road, Jinan 250012, Shandong Province, China.
Li
Lingbing
L
Wang
Yuexia
Y
Tan
Yebang
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D006207:Half-Life; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008823:Micelles; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011409:Propylene Glycols / Q000008:administration & dosage*; D011817:Rabbits; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D011092:Polyethylene Glycols; C028098:10-hydroxycamptothecin; D002166:Camptothecin