title: Delivery of water-soluble drugs using acoustically triggered perfluorocarbon double emulsions.
abstract: OBJECTIVE
  Ultrasound can be used to release a therapeutic payload encapsulated within a perfluorocarbon (PFC) emulsion via acoustic droplet vaporization (ADV), a process whereby the PFC phase is vaporized and the agent is released. ADV-generated microbubbles have been previously used to selectively occlude blood vessels in vivo. The coupling of ADV-generated drug delivery and occlusion has therapeutically synergistic potentials.
  
  
  METHODS
  Micron-sized, water-in-PFC-in-water (W(1)/PFC/W(2)) emulsions were prepared in a two-step process using perfluoropentane (PFP) or perfluorohexane (PFH) as the PFC phase. Fluorescein or thrombin was contained in the W(1) phase.
  
  
  RESULTS
  Double emulsions containing fluorescein in the W(1) phase displayed a 5.7±1.4-fold and 8.2±1.3-fold increase in fluorescein mass flux, as measured using a Franz diffusion cell, after ADV for the PFP and PFH emulsions, respectively. Thrombin was stably retained in four out of five double emulsions. For three out of five formulations tested, the clotting time of whole blood decreased, in a statistically significant manner (p < 0.01), when incubated with thrombin-loaded emulsions exposed to ultrasound compared to emulsions not exposed to ultrasound.
  
  
  CONCLUSIONS
  ADV can be used to spatially and temporally control the delivery of water-soluble compounds formulated in PFC double emulsions. Thrombin release could extend the duration of ADV-generated, microbubble occlusions.
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA. mfabiill@umich.edu
authors.forename: Mario L
authors.initials: ML
authors.lastname: Fabiilli
authors.forename: James A
authors.initials: JA
authors.lastname: Lee
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Kripfgans
authors.forename: Paul L
authors.initials: PL
authors.lastname: Carson
authors.forename: J Brian
authors.initials: JB
authors.lastname: Fowlkes
mesh_terms: D000162:Acoustics; D016503:Drug Delivery Systems; D004655:Emulsions; D019793:Fluorescein / Q000737:chemistry; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000138:chemical synthesis
chemical_list: D004655:Emulsions; D005466:Fluorocarbons; D013501:Surface-Active Agents; D019793:Fluorescein