A novel nested liposome drug delivery vehicle capable of ultrasound triggered release of its payload

Stuart Ibsen, Michael Benchimol, Dmitri Simberg, Carolyn Schutt, Jason Steiner, Sadik Esener

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


The use of focused ultrasound can be an effective method to locally highlight tumor tissue and specifically trigger the activation of echogenic drug delivery vehicles in an effort to reduce systemic chemotherapy side effects. Here we demonstrate a unique ultrasound triggered vehicle design and fabrication method where the payload and a perfluorocarbon gas microbubble are both encapsulated within the internal aqueous space of a liposome. This nested lipid shell geometry both stabilized the microbubble and ensured it was spatially close enough to interact with the liposome membrane at all times. The internal microbubble was shown to fragment the outer liposome membrane upon exposure to ultrasound at intensities of 1-1.5 MPa. The focused ultrasound allowed the release of the internal payload to localized regions within tissue phantoms. The vehicles showed high payload loading efficiency of 16%, stability in blood of several hours, and low level macrophage recognition in vitro. High speed fluorescent videos present the first optical images of such vehicles interacting with ultrasound. This ability to open the outer membrane in small regions of deep tissue could provide a second level of spatial and temporal control beyond biochemical targeting, making these particles promising for in vivo animal studies.

Original languageEnglish (US)
Pages (from-to)358-366
Number of pages9
JournalJournal of Controlled Release
Issue number3
StatePublished - Nov 7 2011
Externally publishedYes


  • Burst release
  • Focused ultrasound
  • Microbubbles
  • Triggered drug delivery
  • Ultrasound triggered release

ASJC Scopus subject areas

  • Pharmaceutical Science


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