title: Cationic amphiphilic drugs self-assemble to the core-shell interface of PEGylated phospholipid micelles and stabilize micellar structure.
abstract: Since polymeric micelles are promising and have potential in drug delivery systems, people have become more interested in studying the compatibility of polymeric carriers and drugs, which might help them to simplify the preparation method and increase the micellar stability. In this article, we report that cationic amphiphilic drugs can be easily encapsulated into PEGylated phospholipid (PEG-PE) micelles by self-assembly method and that they show high encapsulation efficiency, controllable drug release and better micellar stability than empty micelles. The representative drugs are doxorubicin and vinorelbine. However, gemcitabine and topotecan are not suitable for PEG-PE micelles due to lack of positive charge or hydrophobicity. Using a series of experiments and molecular modelling, we figured out the assembly mechanism, structure and stability of drug-loaded micelles, and the location of drugs in micelles. Integrating the above information, we explain the effect of the predominant force between drugs and polymers on the assembly mechanism and drug release behaviour. Furthermore, we discuss the importance of pKa and to evaluate the compatibility of drugs with PEG-PE in self-assembly preparation method. In summary, this work provides a scientific understanding for the reasonable designing of PEG-PE micelle-based drug encapsulation and might enlighten the future study on drug-polymer compatibility for other polymeric micelles.
authors.affiliation: Protein and Peptide Pharmaceutical Laboratory, National Laboratory of Biomacromolecules, Institute of Biophysics, Beijing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Xueqing
authors.initials: X
authors.lastname: Xing
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Fang
authors.forename: Chang
authors.initials: C
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Wu
authors.forename: Jizhong
authors.initials: J
authors.lastname: Lou
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
mesh_terms: D002412:Cations; D004058:Diffusion; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D008422:Materials Testing; D008823:Micelles; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D002412:Cations; D008823:Micelles; D053769:Nanocapsules; D004364:Pharmaceutical Preparations; D010743:Phospholipids; D011092:Polyethylene Glycols
keywords: PEGylated phospholipid micelles; drug–polymer compatibility; fluorescence resonance energy transfer; molecular dynamics simulation; small-angle X-ray scattering