Pluronic L61 Accelerates Flip–Flop and Transbilayer Doxorubicin Permeation

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.

Biophysics in cancer: The relevance of drug-membrane interaction studies

“…In fact, other studies demonstrated that while polyoxyethylene surfactants reversed MDR and also decreased lipid fluidity in plasma membrane vesicles from MDR cells, surfactants that did not reverse MDR did not influence membrane fluidity [149]. Moreover, low concentrations of Pluronic 61 were found to greatly increase the rates of phospholipid flip-flop and transbilayer movement of doxorubicin in lipid bilayers [150].…”

Beta-casein nanocarriers of celecoxib for improved oral bioavailability

“…Increased uptake of polymeric micelles as a result of direct effects, such as increase in membrane permeability and/ or inhibition of P-gp efflux pump, has been reported (35). Membrane fluidity could also be affected, as demonstrated for pluronic micelles (40). Soluble amphiphiles, or detergents, are known to produce structural and dynamic effects on membranes, even at low concentrations.…”

Self-assembling Pluronic®-modified polycations in gene delivery

“…1). This is likely because surfactants such as Pluronics can fuse with the cell membranes, thus affecting their microviscosity, which leads to an enhancement of the transmembrane transport that is likely involved in the transfection mechanism [43]. Nanogels based on P85-g-PEI fused into the endosomal membrane, i.e., possessed distinct membranotropic features [42].…”