Aggregation of phospholipid vesicles by water-soluble polymers

Abstract

Water-soluble polymers such as dextran and polyethylene glycol are known to induce aggregation and size growth of phospholipid vesicles. The present study addresses the dependence of these processes on vesicle size and concentration, polymer molecular weight, temperature, and compartmentalization of the vesicles and polymers, using static and dynamic light scattering. Increasing the molecular weight of the polymers resulted in a reduction of the concentration of polymer needed for induction of aggregation of small unilamellar vesicles. The aggregation was fully reversible (by dilution), within a few seconds, up to a polymer concentration of at least 20 wt %. At relatively low phosphatidylcholine (PC) concentrations (up to approximately 1 mM), increasing the PC concentration resulted in faster kinetics of aggregation and reduced the threshold concentration of polymer required for rapid aggregation (CA). At higher PC concentrations, CA was only slightly dependent on the concentration of PC and was approximately equal to the overlapping concentration of the polymer (C*). The extent of aggregation was similar at 37 and 4 degrees C. Aggregation of large unilamellar vesicles required a lower polymer concentration, probably because aggregation occurs in a secondary minimum (without surface contact). In contrast to experiments in which the polymers were added directly to the vesicles, dialysis of the vesicles against polymer-containing solutions did not induce aggregation. Based on this result, it appears that exclusion of polymer from the hydration sphere of vesicles and the consequent depletion of polymer molecules from clusters of aggregated vesicles play the central role in the induction of reversible vesicle aggregation. The results of all the other experiments are consistent with this conclusion.

Modified Protocols for Surfactant Therapy in Experimental Meconium Aspiration Syndrome

“…There were no significant differences thereafter. Dextran probably improves adsorption rate by promoting fusion of phospholipid membranes [17,18], but does not influence equilibrium surface tension under the present experimental conditions. During quasistatic surface compression, dextran also lowered Á min .…”

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] .…”

Chitosan Enhances the In Vitro Surface Activity of Dilute Lung Surfactant Preparations and Resists Albumin-Induced Inactivation

“…Both experimental (5,6) and theoretical (28) studies support the notion that the nonionic polymers improve the surface activity of lipid extract surfactant by a depletion-attraction mechanism. It has been demonstrated that in a pure phospholipid vesicle system, PEG at certain molecular weights and concentrations can induce a depletion-attraction force that promotes the formation of large phospholipid aggregates (30). Large aggregates are known to be more surface active than their smaller counterpart both in vitro (31) and in vivo (32).…”