A micellar prodrug of paclitaxel conjugated to cyclotriphosphazene.
A novel water soluble and biodegradable cyclotriphosphazene-paclitaxel conjugate was prepared by reacting 2'-succinyl paclitaxel with cyclotriphosphazenes bearing equimolar glycyl-L-lysine and methoxy poly(ethylene glycol) as side groups. The macromolecular conjugate was found to self-assemble in aqueous solution to form stable micelles with a mean hydrodynamic diameter of 24.7 nm and a low critical micelle concentration of 10 mg/L. The present conjugate exhibited lower than free paclitaxel but reasonably high in vitro cytotoxicity against selected human tumor cells due to their hydrolytic degradation in PBS solution.
Jun
Yong Joo
YJ
Department of Chemistry and Nano Science, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea.
Min
Jee Hyon
JH
Ji
Da Eun
da E
Yoo
Jin Hee
JH
Kim
Ji Hyeon
JH
Lee
Hwa Jeong
HJ
Jeong
Byeongmoon
B
Sohn
Youn Soo
YS
D001673:Biodegradation, Environmental; D004151:Dipeptides / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D010758:Phosphorus / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011355:Prodrugs; D012995:Solubility; D013499:Surface Properties; D014867:Water / Q000737:chemistry*
D004151:Dipeptides; D008823:Micelles; D009943:Organophosphorus Compounds; D011355:Prodrugs; C540148:cyclotriphosphazene-paclitaxel conjugate; D014867:Water; D010758:Phosphorus; D011092:Polyethylene Glycols; C035809:glycyllysine; D017239:Paclitaxel