Effect of water-soluble polymers on the state of aggregation, vesicle size, and phase transformations in mixtures of phosphatidylcholine and sodium cholate

Abstract

The state of aggregation and the steady-state size of mixed aggregates made of phospholipids and surfactants are both determined by the surfactant/lipid ratio in the mixed aggregates (Re). Water-soluble polymers, such as dextrans and polyethylene glycols (PEGs) of different molecular weights, induce reversible aggregation of phospholipid vesicles, mostly due to dehydration of the vesicle surface and depletion forces, and only at much higher concentrations, PEGs (but not dextran) also induce irreversible size growth of the vesicles. Here we show that the water-soluble polymers dextrans and PEGs do not affect the vesicle-micelle phase boundaries in mixtures of phosphatidylcholine and the anionic surfactant sodium cholate. By contrast, these polymers affect markedly the steady-state size of cholate-containing vesicles. As compared with pure phosphatidylcholine vesicles, the cholate-containing vesicles have a lower tendency to undergo polymer-induced aggregation, probably due to the electrostatic repulsion between the negatively charged vesicles, but a higher tendency to undergo irreversible size growth at relatively low polymer concentrations. Such irreversible size growth was observed not only for PEG but also for dextran, which in the absence of cholate is incapable of inducing vesicle size growth. These findings are consistent with the prevailing concept that the polymer-induced size growth is due to the effect of large structural fluctuations in the bilayers of deformed aggregated vesicles, the surface of which is dehydrated by the polymer. The presence of cholate in the bilayers at sufficiently high concentrations induces such fluctuations, yielding irreversible size growth within the clusters of dehydrated vesicles formed upon mixing with polymers.

Dextran or Polyethylene Glycol Added to Curosurf for Treatment of Meconium Lung Injury in Rats

“…This fi nding suggests that differences in polymer effects may occur because of [10,11] although dextran aerosolized into lungs with milk aspiration injury before surfactant treatment, enhances surfactant responses [28] . PEG and dextran induce aggregation of pure lipids [29,30] and we have found that PEG and dextran both increase aggregation of surfactants, a fi nding associated with increased rates of adsorption of surfactant lipids to the surface [31] . Depletion forces acting on lipid vesicles are increased in the presence of polymers, which can enhance rates of adsorption of surfactants from subphase to alveolar surface [15,20] .…”

l-Histidine-based pH-sensitive anticancer drug carrier micelle: Reconstitution and brief evaluation of its systemic toxicity

“…Table 1 summarizes the results of reconstitution study of powders obtained by employing the 'pre-adding' method. Sucrose as a conventional lyoprotectant (Talsma et al, 1997;Abdelwahed et al, 2006;Li et al, 2008),PEGas a solubilizer (Meyuhas and Lichtenberg, 1996;Seo and Choi, 2003), and Pluronic (Donini et al, 2002) as a surfactant were selected as a reconstitution formulations for DPHSM. Adding sucrose did not provide any benefits over the absence of the lyoprotectant, which may be due to the lack of its solubility capacity for hydrophobic agents (data not shown).…”

Physical Properties of Phosphatidylcholine Vesicles Containing Small Amount of Sodium Cholate and Consideration on the Initial Stage of Vesicle Solubilization.

“…5) At a still further increased detergent concentration, the Na-chol-containing vesicles disintegrate into intermediate structures, and finally into mixed micelles. 8,9) As far as intermediate structures are concerned, structural changes from vesicles to perforated vesicles, to discoidal sheets, 10) or to rod-like structures 11) have been reported. As described above, the incorporation of Na-chol into vesicular membranes remarkably influences the structures and properties of PC vesicles.…”