title: Stable and efficient delivery of docetaxel by micelle-encapsulation using a tripodal cyclotriphosphazene amphiphile.
abstract: Docetaxel micelle-encapsulated by a tripodal cyclotriphosphazene amphiphilile [NP(PEG750)(GlyPheLeu)(2)Et](3) (CP750) exhibited outstanding drug-loaded micelle stability in aqueous solution compared with the polymeric micelles assembled from linear block copolymers. Furthermore, docetaxel micelle-encapsulated by CP750 is obtainable in solvent free powder form, which is immediately soluble in any aqueous media including saline and PBS and very stable to photo-degradation even in the room light at room temperature. Although docetaxel micelle-encapsulated by CP750 did not display highly improved pharmacokinetic profile compared with Taxotere currently in clinical use, its in vivo xenograft trials exhibited excellent antitumor efficacy by showing complete tumor regression against the breast cancer cells (MDA-MB-231) at a lower dose of 5mg/kg and better efficacy against gastric cancer cells (MKN-28) compared with Taxotere. Furthermore, according to the comparative acute toxicity study, toxicities associated with Taxotere may be remarkably reduced by micelle-encapsulation of docetaxel using CP750, which afforded a much higher LD(50) value of 75 mg/kg compared with 28 mg/kg of docetaxel in Taxotere. Thus docetaxel micelle-encapsulated by CP750 has entered the stage of preclinical studies.
authors.affiliation: Center for Intelligent Nano-Bio Materials, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-Ku, Seoul 120-750, Republic of Korea.
authors.forename: Yong Joo
authors.initials: YJ
authors.lastname: Jun
authors.forename: Vithal B
authors.initials: VB
authors.lastname: Jadhav
authors.forename: Jee Hyon
authors.initials: JH
authors.lastname: Min
authors.forename: Jin Xin
authors.initials: JX
authors.lastname: Cui
authors.forename: Song Wha
authors.initials: SW
authors.lastname: Chae
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Choi
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Kim
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Choi
authors.forename: Hwa Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Youn Soo
authors.initials: YS
authors.lastname: Sohn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D000077143:Docetaxel; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D008823:Micelles; D010455:Peptides / Q000737:chemistry*; D010782:Photolysis; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013274:Stomach Neoplasms / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D013678:Technology, Pharmaceutical / Q000379:methods; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: C571634:(NP(PEG750)(GlyPheLeu)2Et)3; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; D043823:Taxoids; D000077143:Docetaxel; D011092:Polyethylene Glycols