Pluronic L61 accelerates flip-flop and transbilayer doxorubicin permeation.
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.
Krylova
Oxana O
OO
Department of Chemistry MV Lomonosov Moscow State University Leninskie Gory, 119899 Moscow, Russia.
Melik-Nubarov
Nikolay S
NS
Badun
Gennadii A
GA
Ksenofontov
Alexander L
AL
Menger
Fred M
FM
Yaroslavov
Alexander A
AA
D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry / Q000494:pharmacology; D005027:Ethylene Oxide / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D050356:Lipid Metabolism; D020442:Poloxamer / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
D004852:Epoxy Compounds; D008051:Lipid Bilayers; C480965:pluronic L61; D020442:Poloxamer; D004317:Doxorubicin; D005027:Ethylene Oxide; C009068:propylene oxide