Microbubbles coated with disaturated lipids and DSPE-PEG2000: phase behavior, collapse transitions, and permeability.

Saturated diacyl (disaturated) phosphatidylcholine (PC) mixed with the lipopolymer distearoylphosphatidylethanolamine (DSPE)-polyethyleneglycol molecular weight 2000 (PEG2000) self-assemble as a monolayer at the air-water interface of air-in-water micrometer-scale bubbles (microbubbles), similar to coatings (shells) on leading medical ultrasound contrast agents (UCAs). This system is characterized here to study the impact of the DSPE-PEG2000 species and PC chain-length on the monolayer coating phase behavior, collapse, shedding, and air transport resistance and microbubble dissolution rate and surface contour. Using fluorescence microscopy of dissolving microbubbles, we found that film microstructure and collapse behavior for all chain lengths (n = 14-20) was indicative of primarily condensed phase monolayers, unlike similar coatings containing polyethyleneglycol 40 stearate (PEG40S) that are either expanded phase or coexisting expanded-condensed phase monolayers. Additionally, we observed a new surface buckling type of behavior with all chain lengths, by bright field microscopy, where the air-water interface continuously appears rough (rather than cyclically rough and smooth), with this behavior most frequently observed for n = 16. In correlating the statistical frequency of this behavior with the monolayer microstructure, we propose that it arises from a slowed nucleation rate of collapse structures at condensed-condensed phase interfaces, not present in systems containing PEG40S. By modeling the dissolution (radius vs time) data, we obtained, for each chain length, the film air transport resistance (R(shell)) that was then fit to a chain-length-dependent energy barrier model. Importantly, the pre-exponential factor was approximately 10 x higher and the microbubbles persisted approximately 4 x longer (from 15 microm at a fixed dissolved oxygen content) in comparison to previously studied films containing PEG40S. We attribute the unique stability properties of microbubble coatings containing DSPE-PEG2000 to the propensity of this molecule to form a condensed-phase monolayer, such that the monolayer coatings approach the properties of one continuous condensed domain.