title: Pegylated phospholipids-based self-assembly with water-soluble drugs.
abstract: OBJECTIVE
  To investigate the self-assembly of polyethylene glycol (PEG)-phosphatidylethanolamine (PE) conjugate with water-soluble drugs (doxorubicin hydrochloride, vinorelbine tartrate and vincristine sulfate) and give insight into the mechanism of formation and mode of interaction of the drug with PEG-PE as well as the general principles of self-assembly using pegylated lipid micelles.
  
  
  METHODS
  One-step self-assembly method to prepare drug-loaded micelles was developed. The micelles were characterized by dynamic light scattering, transmission electron microscopy, encapsulation efficiency, and release study. NMR was used to study molecular assembly of PEG-PE with doxorubicin.
  
  
  RESULTS
  Doxorubicin hydrochloride and vinorelbine tartrate were entrapped into micelles with high efficiency of >99.0% at molar ratios of 1:1 and 2:1 of PEG-PE to drugs, respectively. Drug loading did not measurably perturb either the geometry or the size. It was found that electrostatic interaction and hydrophobic forces are responsible for the intercalation of drugs into PEG-PE micelles. NMR data revealed that the anthracycline ring of doxorubicin was inserted between PE phospholipids, and its amino sugar located in the outer shell of micelle between PEG chains.
  
  
  CONCLUSIONS
  Based on our results, the structure and self-assembly mechanism of water-soluble drugs encapsulated in PEG-PE micelles were proposed.
authors.affiliation: Protein & Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ruiqi
authors.initials: R
authors.lastname: Wang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.forename: Wanliang
authors.initials: W
authors.lastname: Lu
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry* / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility / Q000187:drug effects; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D010743:Phospholipids; D014867:Water; D011092:Polyethylene Glycols