Effect of PEO−PPO−PEO Triblock Copolymers on Structure and Stability of Phosphatidylcholine Liposomes

Abstract

The interactions of five poly(oxyethylene)−poly(oxypropylene)−poly(oxyethylene) (PEO−PPO−PEO), Pluronic, copolymers and phosphatidylcholine liposomes of varying composition have been studied. Structural studies were performed by means of cryo-transmission electron microscopy (c-TEM) and reveal that inclusion of low amounts (∼2 mol %) of Pluronics gives rise to significant morphological changes of the liposome preparations. Pluronics with large poly(oxyethylene) (PEO) blocks, such as F127, F108, and F87, induce the formation of bilayer disks, whereas those with comparably short PEO blocks, P105 and P85, tend to to promote a reduction in the liposome size. Inclusion of cholesterol in the liposomal preparations reduces the incorporation of copolymers in the lipid bilayer and thus reduces, and in some cases even abolishes, the morphological changes observed in the absence of cholesterol. The effect of the copolymers on liposome permeability was also investigated. All investigated copolymers were found to increase the leakage of carboxyfluorescein from preformed liposomes. This was true also in the case of cholesterol-containing liposomes despite the fact that no change in the liposome structure could be observed by means of c-TEM. The magnitude of the induced leakage was found to correlate well with the hydrophobicity, as measured by the cmc, of the respective Pluronic. By raising the temperature or decreasing the solvency of the copolymer in the solution, the effect of the copolymer on liposome leakage was found to increase significantly.