title: PEG-detachable and acid-labile cross-linked micelles based on orthoester linked graft copolymer for paclitaxel release.
abstract: Polyethylene glycol detachable graft copolymer, mPEG-g-p(NAS-co-BMA), was synthesized by grafting 2-(ω-methoxy)PEGyl-1,3-dioxan-5-ylamine onto poly(N-(acryloyloxy)succinimide-co-butyl methacrylate). Pseudo in situ cross-linking of the mPEG-g-p(NAS-co-BMA) was performed in dimethylformamide phosphate buffer (v/v = 1/1) by an acid-labile diamine cross-linker bearing two symmetrical cyclic orthoesters. The cross-linked (CL) micelles with different contents of mPEG segments represented different morphologies. The CL micelles containing approximately one mPEG segment exhibited 'echini' morphology whereas the CL micelle with approximately three mPEG segments formed nanowires. The hydrolysis rate of the CL micelles is highly pH-dependent and much more rapid at mild acid than physiological conditions. Hydrolyzates of the CL micelles formed vesicles because new amphiphilic copolymers were formed. Paclitaxel (PTX) was successfully loaded into the CL micelles and a controlled and pH-dependent release behavior was observed. No obvious cytotoxicity was found for the CL micelles at concentration as high as 800  mg l( - 1).
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Science, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Zhefan
authors.initials: Z
authors.lastname: Yuan
authors.forename: Jingyi
authors.initials: J
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Sixue
authors.initials: S
authors.lastname: Cheng
authors.forename: Renxi
authors.initials: R
authors.lastname: Zhuo
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000143:Acids / Q000737:chemistry*; D000818:Animals; D019556:COS Cells; D016923:Cell Death / Q000187:drug effects; D002522:Chlorocebus aethiops; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006868:Hydrolysis / Q000187:drug effects; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D017239:Paclitaxel / Q000494:pharmacology*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D058105:Polymerization / Q000187:drug effects; D012542:Scattering, Radiation; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000143:Acids; D003432:Cross-Linking Reagents; D004952:Esters; D008823:Micelles; D011092:Polyethylene Glycols; D017239:Paclitaxel