title: PEG-stabilized micellar system with positively charged polyester core for fast pH-responsive drug release.
abstract: OBJECTIVE
  To design functional drug carriers for fast pH-responsive drug release.
  
  
  METHODS
  Functional diblock terpolymers of monomethoxy poly(ethylene glycol)-block- copoly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione-co-ε-caprolactone) [mPEG-b-poly(ADMC-co-CL)] were fabricated via biosynthetic pathway. The self-assembled nanosphere and drug-loaded micelles of the copolymers were further prepared by dialysis method. The pH-tunable morphology variation and drug release pattern were observed at different pH.
  
  
  RESULTS
  A collection of three PEGylated terpolymers with varied compositions in poly(ADMC-co-CL) block was designed with high cell-biocompatibility. The copolymers could readily self-assemble into nanoscale micelles (~ 100 nm) in aqueous medium and exhibit high stability over 80-h incubation in different mediums including deionized water, neutral NaCl solution, and heparin sodium solution. Due to the protonation-deprotonation of tertiary amine groups in ADMC units, acid-induced structural deformation of micelles was disclosed in terms of the variation in CAC value and hydrodynamic size at different pH. Drug loading efficiency was comparable to that of reported PEG-polyester micelles with specifically designed structures purposed for drug-loading improvement. Remarkably accelerated drug release triggered by acidity was distinctly detected for ibuprofen-loaded mPEG-b-poly(ADMC-co-CL) micelle system, suggesting a fast pH-responsive characteristic.
  
  
  CONCLUSIONS
  Functional PEG-stabilized micellar carriers with positively charged polyester core were successfully developed for fast pH-responsive drug release.
authors.affiliation: Key Laboratory of Biomedical Polymers, The Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, China.
authors.forename: Hua-Fen
authors.initials: HF
authors.lastname: Wang
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Jia
authors.forename: Si-Xue
authors.initials: SX
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Xian-Zheng
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D001672:Biocompatible Materials; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002522:Chlorocebus aethiops; D003956:Dialysis; D004337:Drug Carriers; D004339:Drug Compounding; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007052:Ibuprofen / Q000737:chemistry*; D007700:Kinetics; D008823:Micelles; D054118:Nanospheres; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; C574289:monomethoxy poly(ethylene glycol)-block-copoly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diazacyclohexadecane-2,10-dione-co-epsilon-caprolactone); D011092:Polyethylene Glycols; D007052:Ibuprofen