title: An evaluation of the sonoporation potential of low-boiling point phase-change ultrasound contrast agents in vitro.
abstract: BACKGROUND
  Phase-change ultrasound contrast agents (PCCAs) offer a solution to the inherent limitations associated with using microbubbles for sonoporation; they are characterized by prolonged circulation lifetimes, and their nanometer-scale sizes may allow for passive accumulation in solid tumors. As a first step towards the goal of extravascular cell permeabilization, we aim to characterize the sonoporation potential of a low-boiling point formulation of PCCAs in vitro.
  
  
  METHODS
  Parameters to induce acoustic droplet vaporization and subsequent microbubble cavitation were optimized in vitro using high-speed optical microscopy. Sonoporation of pancreatic cancer cells in suspension was then characterized at a range of pressures (125-600 kPa) and pulse lengths (5-50 cycles) using propidium iodide as an indicator molecule.
  
  
  RESULTS
  We achieved sonoporation efficiencies ranging from 8 ± 1% to 36 ± 4% (percent of viable cells), as evidenced by flow cytometry. Increasing sonoporation efficiency trended with increasing pulse length and peak negative pressure.
  
  
  CONCLUSIONS
  We conclude that PCCAs can be used to induce the sonoporation of cells in vitro, and our results warrant further investigation into the use of PCCAs as extravascular sonoporation agents in vivo.
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina Chapel Hill, Chapel Hill, NC USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Fix
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina Chapel Hill and North Carolina State University, Chapel Hill, NC USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Novell
authors.affiliation: FIT BEST Laboratory, Chemical, Biological and Bioengineering Department, North Carolina A&T State University, Greensboro, NC USA.
authors.forename: Yeoheung
authors.initials: Y
authors.lastname: Yun
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina Chapel Hill, Chapel Hill, NC USA.|Joint Department of Biomedical Engineering, University of North Carolina Chapel Hill and North Carolina State University, Chapel Hill, NC USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Dayton
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina Chapel Hill and North Carolina State University, Chapel Hill, NC USA.|Laboratory for Therapeutic Directed Energy, Department of Physics, Elon University, Elon, NC USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Arena
keywords: Acoustic droplet vaporization; Drug delivery; Nanodroplet; Sonoporation; Ultrasound