Delivery of water-soluble drugs using acoustically triggered perfluorocarbon double emulsions.
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.
Fabiilli
Mario L
ML
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA. mfabiill@umich.edu
Lee
James A
JA
Kripfgans
Oliver D
OD
Carson
Paul L
PL
Fowlkes
J Brian
JB
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
D004655:Emulsions; D005466:Fluorocarbons; D013501:Surface-Active Agents; D019793:Fluorescein