title: Duration of ultrasound-mediated enhanced plasma membrane permeability.
abstract: Ultrasound (US) induced cavitation can be used to enhance the intracellular delivery of drugs by transiently increasing the cell membrane permeability. The duration of this increased permeability, termed temporal window, has not been fully elucidated. In this study, the temporal window was investigated systematically using an endothelial- and two breast cancer cell lines. Model drug uptake was measured as a function of time after sonication, in the presence of SonoVue™ microbubbles, in HUVEC, MDA-MB-468 and 4T1 cells. In addition, US pressure amplitude was varied in MDA-MB-468 cells to investigate its effect on the temporal window. Cell membrane permeability of HUVEC and MDA-MB-468 cells returned to control level within 1-2 h post-sonication, while 4T1 cells needed over 3h. US pressure affected the number of cells with increased membrane permeability, as well as the temporal window in MDA-MB-468 cells. This study shows that the duration of increased membrane permeability differed between the cell lines and US pressures used here. However, all were consistently in the order of 1-3 h after sonication.
authors.affiliation: Imaging Division, University Medical Center Utrecht, Utrecht, Netherlands. Electronic address: b.h.a.lammertink@umcutrecht.nl.
authors.forename: Bart
authors.initials: B
authors.lastname: Lammertink
authors.affiliation: Imaging Division, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Deckers
authors.affiliation: Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Targeted Therapeutics, University of Twente, Enschede, Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Imaging Division, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Chrit
authors.initials: C
authors.lastname: Moonen
authors.affiliation: Imaging Division, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Clemens
authors.initials: C
authors.lastname: Bos
mesh_terms: D001562:Benzimidazoles / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D005260:Female; D006801:Humans; D045423:Microbubbles; D009930:Organic Chemicals / Q000378:metabolism; D013010:Sonication; D013997:Time Factors; D000069453:Ultrasonic Waves
chemical_list: D001562:Benzimidazoles; D009930:Organic Chemicals; C402795:SYTOX Green; C017807:bisbenzimide ethoxide trihydrochloride
keywords: Drug delivery; Fluorescent model drug; Membrane permeabilization; Microbubbles; Sonoporation; Ultrasound