Pharmaceutical Research

, Volume 27, Issue 12, pp 2753–2765

Delivery of Water-Soluble Drugs Using Acoustically Triggered Perfluorocarbon Double Emulsions

  • Mario L. Fabiilli
  • James A. Lee
  • Oliver D. Kripfgans
  • Paul L. Carson
  • J. Brian Fowlkes
Research Paper

DOI: 10.1007/s11095-010-0277-5

Cite this article as:
Fabiilli, M.L., Lee, J.A., Kripfgans, O.D. et al. Pharm Res (2010) 27: 2753. doi:10.1007/s11095-010-0277-5

ABSTRACT

Purpose

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 (W1/PFC/W2) 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 W1 phase.

Results

Double emulsions containing fluorescein in the W1 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.

KEY WORDS

acoustic droplet vaporization double emulsion embolization perfluorocarbon thrombin ultrasound vascular occlusion 

ABBREVIATIONS

ACT

activated clotting time

ADV

acoustic droplet vaporization

CPD

citrate-phosphate-dextrose

IU

international units

PEG

polyethylene glycol

PFC

perfluorocarbon

PFH

perfluoro-n-hexane

PFP

perfluoro-n-pentane

PRP

pulse repetition period

US

ultrasound

W1/PFC/W2

water-in-perfluorocarbon-in-water

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Mario L. Fabiilli
    • 1
    • 2
    • 4
  • James A. Lee
    • 2
  • Oliver D. Kripfgans
    • 1
    • 2
    • 3
  • Paul L. Carson
    • 1
    • 2
  • J. Brian Fowlkes
    • 1
    • 2
  1. 1.Department of Biomedical EngineeringUniversity of MichiganAnn ArborUSA
  2. 2.Department of RadiologyUniversity of MichiganAnn ArborUSA
  3. 3.Applied Physics ProgramUniversity of MichiganAnn ArborUSA
  4. 4.Ann ArborUSA