Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound

Paul S. Sheeran, Samantha Luois, Paul A. Dayton, Terry O Matsunaga

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

Recent efforts in the area of acoustic droplet vaporization with the objective of designing extravascular ultrasound contrast agents has led to the development of stabilized, lipid-encapsulated nanodroplets of the highly volatile compound decafluorobutane (DFB). We developed two methods of generating DFB droplets, the first of which involves condensing DFB gas (boiling point from -1.1 to -2 °C) followed by extrusion with a lipid formulation in HEPES buffer. Acoustic droplet vaporization of micrometer-sized lipid-coated droplets at diagnostic ultrasound frequencies and mechanical indices were confirmed optically. In our second formulation methodology, we demonstrate the formulation of submicrometer-sized lipid-coated nanodroplets based upon condensation of preformed microbubbles containing DFB. The droplets are routinely in the 200-300 nm range and yield microbubbles on the order of 1-5 μm once vaporized, consistent with ideal gas law expansion predictions. The simple and effective nature of this methodology allows for the development of a variety of different formulations that can be used for imaging, drug and gene delivery, and therapy. This study is the first to our knowledge to demonstrate both a method of generating ADV agents by microbubble condensation and formulation of primarily submicrometer droplets of decafluorobutane that remain stable at physiological temperatures. Finally, activation of DFB nanodroplets is demonstrated using pressures within the FDA guidelines for diagnostic imaging, which may minimize the potential for bioeffects in humans. This methodology offers a new means of developing extravascular contrast agents for diagnostic and therapeutic applications.

Original languageEnglish (US)
Pages (from-to)10412-10420
Number of pages9
JournalLangmuir
Volume27
Issue number17
DOIs
StatePublished - Sep 6 2011

Fingerprint

Phase shift
phase shift
Ultrasonics
Acoustics
lipids
formulations
Lipids
acoustics
methodology
Vaporization
Contrast Media
condensation
Condensation
Gases
condensing
HEPES
Imaging techniques
ideal gas
genes
boiling

ASJC Scopus subject areas

  • Electrochemistry
  • Condensed Matter Physics
  • Surfaces and Interfaces
  • Materials Science(all)
  • Spectroscopy

Cite this

Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound. / Sheeran, Paul S.; Luois, Samantha; Dayton, Paul A.; Matsunaga, Terry O.

In: Langmuir, Vol. 27, No. 17, 06.09.2011, p. 10412-10420.

Research output: Contribution to journalArticle

Sheeran, Paul S. ; Luois, Samantha ; Dayton, Paul A. ; Matsunaga, Terry O. / Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound. In: Langmuir. 2011 ; Vol. 27, No. 17. pp. 10412-10420.
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