A method for radiation-force localized drug delivery using gas-filled lipospheres

Michaelann J. Shortencarier, Paul A. Dayton, Susannah H. Bloch, Patricia A. Schumann, Terry O Matsunaga, Katherine W. Ferrara

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

We have developed a method using ultrasound and acoustically active lipospheres (AALs) that might be used to deliver bioactive substances to the vascular endothelium. The AALs consist of a small gas bubble surrounded by a thick oil shell and enclosed by an outermost lipid layer. The AALs are similar to ultrasound contrast agents: they can be nondestructively deflected using ultrasound radiation force, and fragmented with high-intensity ultrasound pulses. The lipid-oil complex might be used to carry bioactive substances at high concentrations. An optimized sequence of ultrasound pulses can deflect the AALs toward a vessel wall then disrupt them, painting their contents across the vascular endothelium. This paper presents results from a series of in vitro and ex vivo experiments demonstrating localization of a fluorescent model drug. In experiments using a human melanoma cell (A2085) monolayer, a specific radiation force-fragmentation ultrasound pulse sequence increased cell fluorescence more than 10-fold over no ultrasound or fragmentation pulses alone, and by 50% over radiation force pulses alone. We observe that dye transfer is limited to cells that are in the region of ultrasonic focus, indicating that the application of radiation force pulses to bring the delivery vehicle into proximity with the cell is required for successful adhesion of the vehicle fragments to the cell membrane. We also demonstrate dye transfer from flowing AALs, both in a mimetic vessel and in excised rat cecum. We believe that this method could be successfully used for drug delivery in vivo.

Original languageEnglish (US)
Pages (from-to)822-831
Number of pages10
JournalIEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
Volume51
Issue number7
StatePublished - Jul 2004
Externally publishedYes

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Drug delivery
delivery
drugs
Ultrasonics
Radiation
radiation
pulses
Gases
gases
endothelium
activity (biology)
cells
vessels
lipids
fragmentation
vehicles
oils
dyes
Lipids
Dyes

ASJC Scopus subject areas

  • Electrical and Electronic Engineering
  • Acoustics and Ultrasonics

Cite this

A method for radiation-force localized drug delivery using gas-filled lipospheres. / Shortencarier, Michaelann J.; Dayton, Paul A.; Bloch, Susannah H.; Schumann, Patricia A.; Matsunaga, Terry O; Ferrara, Katherine W.

In: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control, Vol. 51, No. 7, 07.2004, p. 822-831.

Research output: Contribution to journalArticle

Shortencarier, Michaelann J. ; Dayton, Paul A. ; Bloch, Susannah H. ; Schumann, Patricia A. ; Matsunaga, Terry O ; Ferrara, Katherine W. / A method for radiation-force localized drug delivery using gas-filled lipospheres. In: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control. 2004 ; Vol. 51, No. 7. pp. 822-831.
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