Dynamics and fragmentation of thick-shelled microbubbles

Donovan J. May, John S. Allen, Katherine W. Ferrara

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


Localized delivery could decrease the systemic side effects of toxic chemotherapy drugs. The unique delivery agents we examine consist of microbubbles with an outer lipid coating, an oil layer, and a perfluorobutane gas core. These structures are 0.5-12 μm in radius at rest. Oil layers of these acoustically active lipospheres (AALs) range from 0.3-1.5 μm in thickness and thus the agents can carry a large payload compared to nano-scale drug delivery systems. We show that triacetin-based drug-delivery vehicles can be fragmented using ultrasound. Compared with a lipid-shelled contrast agent, the expansion of the drug-delivery vehicle within the first cycle is similar, and a subharmonic component is demonstrated at an equivalent radius, frequency, and driving pressure. For the experimental conditions explored here, the pulse length required for destruction of the drug-delivery vehicle is significantly greater, with at least five cycles required, compared with one cycle for the contrast agent. For the drug-delivery vehicle, the observed destruction mechanism varies with the initial radius, with microbubbles smaller than resonance size undergoing a symmetric collapse and producing a set of small, equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents larger than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.

Original languageEnglish (US)
Pages (from-to)1400-1410
Number of pages11
JournalIEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
Issue number10
StatePublished - Oct 2002

ASJC Scopus subject areas

  • Electrical and Electronic Engineering
  • Acoustics and Ultrasonics


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