Physico-chemical properties of the microbubble lipid shell: Composition, microstructure & properties of targeted ultrasound contrast agents

Mark A. Borden, Paul Dayton, Shukui Zhao, Katherine W. Ferrara

Research output: Chapter in Book/Report/Conference proceedingConference contribution

22 Scopus citations


Targeted microbubbles stabilized by a lipid monolayer are currently being developed in conjunction with ultrasound for diagnostic and therapeutic applications. Targeted microbubbles utilize specific receptor-ligand interactions to adhere to the site of interest - a process which can be enhanced by using ultrasonic radiation force. The monolayer shell is composed of a main phospholipid component and an emulsifier comprising a poly(ethylene glycol) (PEG) headgroup. The targeting ligand is tethered to a lipid in the monolayer via a PEG spacer. The monolayer shell is typically represented as a uniform film, in which the components are fully miscible. Recent studies, however, have shown that the shell is indeed polycrystalline and exhibits lateral phase separation whereby the lipid forms crystalline domains surrounded by a less ordered, entulsifier-rich expanded phase region. We use epi-fluorescence microscopic techniques to show that the targeting ligand is also excluded from the lipid domains and enriched in the expanded phase, thus yielding a heterogeneous surface distribution that is dependent upon microstructure. We also show that lipid composition plays a crucial role in the fate of the lipid shell during intermittent insonation. The shell was more cohesive in the case of the single hydrophobic chain emulsifier than the double hydrophobic chain homologue. An increase in the phospholipid acyl chain length, for a given emulsifier, resulted in a more cohesive shell due to increased lateral dispersion forces. Four mechanisms for shedding of excess lipid are presented to account for the observed differences in shell cohesiveness. Our results indicate that shell composition and microstructure will affect properties relevant to acoustic response, targeted adhesion efficiency and delivery of shell-associated therapeutic agents.

Original languageEnglish (US)
Title of host publicationProceedings - IEEE Ultrasonics Symposium
EditorsM.P. Yuhas
Number of pages4
StatePublished - 2004
Event2004 IEEE Ultrasonics Symposium - Montreal, Que., Canada
Duration: Aug 23 2004Aug 27 2004


Other2004 IEEE Ultrasonics Symposium
CityMontreal, Que.


  • Phospholipid monolayer microstructure
  • Shell shedding
  • Targeting ligand location
  • Ultrasound contrast agent

ASJC Scopus subject areas

  • Engineering(all)


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