Pluronic L61 accelerates flip-flop and transbilayer doxorubicin permeation

Chemistry. 2003 Aug 18;9(16):3930-6. doi: 10.1002/chem.200204621.

Abstract

It has recently been found that Pluronics (block copolymers of ethylene oxide, EO, and propylene oxide, PO) favor the permeability and accumulation of anthracycline antibiotics, for example doxorubicin (Dox), in tumor cells. In an effort to understand these results, the interaction of EO(2)/PO(32)/EO(2) (Pluronic L61) with unilamellar egg yolk vesicles (80-100 nm in diameter) was examined. A partition coefficient K(p)=[Pl](membrane)/[Pl](water)=45 was determined. This corresponds to adsorption of about 20 polymer molecules to the surface of each vesicle in a 20 microM polymer solution. Despite this rather weak adsorption, Pluronic has a substantial effect upon the transmembrane permeation rate of Dox and upon the phospholipid flip-flop rate within the bilayers. Thus, the Dox permeation rate increases threefold and the flip-flop rate increases sixfold in 20 microM Pluronic. The two rates increase linearly with the amount of adsorbed polymer. The obvious ability of Pluronics to increase the mobility of membrane components may have important biomedical consequences.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Biological Transport / drug effects
  • Cell Membrane Permeability / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism*
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / pharmacology
  • Ethylene Oxide / chemistry
  • Ethylene Oxide / pharmacology
  • Kinetics
  • Lipid Bilayers / chemistry*
  • Lipid Bilayers / metabolism
  • Lipid Metabolism
  • Poloxamer / chemistry
  • Poloxamer / pharmacology*
  • Structure-Activity Relationship
  • Time Factors

Substances

  • Epoxy Compounds
  • Lipid Bilayers
  • pluronic L61
  • Poloxamer
  • Doxorubicin
  • Ethylene Oxide
  • propylene oxide