Pegylated phospholipids-based self-assembly with water-soluble drugs.
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.
Wang
Yiguang
Y
Protein & Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Wang
Ruiqi
R
Lu
Xiaoyan
X
Lu
Wanliang
W
Zhang
Chunling
C
Liang
Wei
W
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
D004364:Pharmaceutical Preparations; D010743:Phospholipids; D014867:Water; D011092:Polyethylene Glycols