title: Synthesis of three-arm block copolymer poly(lactic-co-glycolic acid)-poly(ethylene glycol) with oxalyl chloride and its application in hydrophobic drug delivery.
abstract: OBJECTIVE
  Synthesis of star-shaped block copolymer with oxalyl chloride and preparation of micelles to assess the prospect for drug-carrier applications.
  
  
  METHODS
  Three-arm star block copolymers of poly(lactic-co-glycolic acid) (3S-PLGA)-polyethylene glycol (PEG) were synthesized by ring-opening polymerization, then PEG as the hydrophilic block was linked to the terminal hydroxyl of 3S-PLGA with oxalyl chloride. Fourier-transform infrared (FT-IR) spectroscopy, gel-permeation chromatography (GPC), hydrogen nuclear magnetic resonance (1H-NMR) spectra, and differential scanning calorimetry were employed to identify the structure and properties of 3S-PLGA-PEG. Rapamycin (RPM)-loaded micelles were prepared by solvent evaporation, and pyrene was used as the fluorescence probe to detect the critical micelle concentration of the copolymer. The particle size, distribution, and ζ-potential of the micelles were determined by dynamic light scattering, and the morphology of the RPM-loaded micelles was analyzed by transmission electron microscopy. High-performance liquid chromatography was conducted to analyze encapsulation efficiency and drug-loading capacity, as well as the release behavior of RPM-loaded micelles. The biocompatibility of material and the cytostatic effect of RPM-loaded micelles were investigated by Cell Counting Kit 8 assay.
  
  
  RESULTS
  FT-IR, GPC, and1H-NMR suggested that 3S-PLGA-PEG was successfully synthesized. The RPM-loaded micelles prepared with the 3S-PLGA-PEG possessed good properties. The micelles had good average diameter and encapsulation efficiency. For in vitro release, RPM was released slowly from 3S-PLGA-PEG micelles, showing that 3S-PLGA-PEG-RPM exhibited a better and longer antiproliferative effect than free RPM.
  
  
  CONCLUSIONS
  In this study, we first used oxalyl chloride as the linker to synthesize 3S-PLGA-PEG successfully, and compared with reported literature, this method shortened the reaction procedure and improved the reaction yield. The micelles prepared with this material proved suitable for drug-carrier application.
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Duan
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liang
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Xuanling
authors.initials: X
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Hongfan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D002712:Chlorides / Q000737:chemistry*; D002849:Chromatography, Gas; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry; D006016:Glycolates / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010070:Oxalates / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D058105:Polymerization; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D002712:Chlorides; D004337:Drug Carriers; D005456:Fluorescent Dyes; D006016:Glycolates; D008823:Micelles; D010070:Oxalates; C031149:glycolic acid; D011092:Polyethylene Glycols; C092266:oxalyl chloride
keywords: RPM; block copolymer; cytostatic effect; micelles