Evaluation of the temporal window for drug delivery following ultrasound-mediated membrane permeability enhancement.
OBJECTIVE
Ultrasound-induced cavitation facilitates cellular uptake of drugs via increased membrane permeability. Here, the purpose was to evaluate the duration of enhanced membrane permeability following ultrasound treatment in cell culture.


METHODS
Optical chromophores with fluorescence intensity increasing 100-1,000-fold upon intercalation with nucleic acids served as smart agents for reporting cellular uptake. Opticell chambers with a monolayer of C6 cells were subjected to ultrasound in the presence of microbubbles followed by varying delays between 0 and 24 h before addition of Sytox Green optical contrast agent. Micro- and macroscopic fluorescence were used for qualitative and quantitative analysis.


RESULTS
Up to 25% of viable cells showed uptake of contrast agent with a half time of 8 h, with cellular uptake persisting even at 24 h. Only cells exposed to ultrasound showed the effect.


CONCLUSIONS
The temporal window of increased membrane permeability is much longer in these studies than previously suggested. This may have important repercussions for in vivo studies in which membrane permeability may be temporally separated from drug delivery.
Yudina
Anna
A
Laboratory for Molecular and Functional Imaging: from Physiology to Therapy, UMR5231 CNRS/University Victor Segalen Bordeaux, 146 rue Leo Saignat, Case 117, 33076, Bordeaux, France. anna@imf.u-bordeaux2.fr
Lepetit-Coiffé
Matthieu
M
Moonen
Chrit T W
CT
D000818:Animals; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D042541:Intracellular Space / Q000378:metabolism; D009930:Organic Chemicals / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014465:Ultrasonics / Q000379:methods*
D005456:Fluorescent Dyes; D009930:Organic Chemicals; C402795:SYTOX Green