title: Synthesis and characterization of a novel polydepsipeptide contained tri-block copolymer (mPEG-PLLA-PMMD) as self-assembly micelle delivery system for paclitaxel.
abstract: A series of biodegradable polydepsipeptides based new triblock copolymers, poly (ethylene glycol)-poly(L-lactide)-poly(3(S)-methyl-morpholine-2,5-dione) (mPEG-PLLA-PMMD) have been synthesized and characterized as self-assembly micelle delivery system for paclitaxel (PTX). Compared to the mPEG(2000)-PLLA(2000) diblock copolymers, the triblock copolymers present more benefits such as lower CMC value, positive-shifted zeta potential, better drug loading efficiency and stability. Among the triblock polymers, mPEG(2000)-PLLA(2000)-PMMD(1400) micelles present low cytotoxicity and promote the anti-cancer activity of PTX on A-549 and HCT-116cells. In addition, mPEG(2000)-PLLA(2000)-PMMD(1400) micelles prolongs the circulation time of PTX in rat after i.v. injection (5 mg/kg) than that of mPEG(2000)-PLLA(2000) micelles and Taxol. The half life (t(1/2β)), mean residence time (MRT), AUC(0-∞) and clearance (CL) for PTX-loaded mPEG(2000)-PLLA(2000)-PMMD(1400) micelles are determined to be 1.941 h, 2.683 h, 5.220 μg/m Lh (1.8-fold to mPEG(2000)-PLLA(2000) group), 0.967 L/h kg(-1), respectively. In conclusion, mPEG(2000)-PLLA(2000)-PMMD(1400) copolymer could be developed as one of the promising vectors to anti-cancer agents for chemotherapeutics.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Yu
authors.forename: Guangji
authors.initials: G
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003110:Colonic Neoplasms / Q000473:pathology; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D045325:HCT116 Cells; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008657:Metabolic Clearance Rate; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000633:toxicity; D011108:Polymers / Q000138:chemical synthesis* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: C575139:(ethylene glycol)-poly(lactide)-poly(3-methyl-morpholine-2,5-dione); D000972:Antineoplastic Agents, Phytogenic; D047630:Depsipeptides; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011092:Polyethylene Glycols; D017239:Paclitaxel