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1. Ultrasound Med Biol. 2012 Mar 16. [Epub ahead of print]

Increased Accumulation and Retention of Micellar Paclitaxel in Drug-Sensitive and
P-glycoprotein-Expressing Cell Lines Following Ultrasound Exposure.

Wan CP, Jackson JK, Pirmoradi FN, Chiao M, Burt HM.

Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver,
BC, Canada.

Ultrasound treatment has been shown to enhance the uptake of both hydrophilic and
hydrophobic compounds into PC3 and Huvec cell lines using an insonation regimen
of a single 10-s burst of high-frequency (4 MHz), moderate intensity (32 W/cm(2))
ultrasound. The purpose of this work was to evaluate the effect of this
ultrasound regimen on the cellular accumulation of paclitaxel (PTX) loaded in
copolymer micellar of methoxy poly(ethylene glycol)-block-poly(D,L-lactide)
(MePEG-b-PDLLA) in both drug-sensitive (MDCKII and MCF-7) and P-glycoprotein
(Pgp)-expressing (MDCKII-MDR and NCI-ADR) cell lines. There were no effects of
ultrasound on hydrodynamic diameters of micelles and the release of FRET pairs,
indicating the integrity of micelles was maintained. There was a two-fold
increase in intracellular PTX for all ultrasound-treated drug-sensitive cell
lines and their respective drug-resistant counterparts compared with no
ultrasound. Significant decreases in drug efflux rates were observed at 20, 40
and 60 min for both drug-sensitive and -resistant cell lines receiving
ultrasound. The enhanced accumulation and retention of PTX by ultrasound resulted
in greater cytotoxicity in both MDCKII and MDCKII-MDR cell lines, as indicated by
the MTS assay. These data suggest that ultrasound may facilitate the uptake of
intact paclitaxel-loaded micelles into cells, allowing greater retention of drug
in both Pgp and non-Pgp-expressing cells.

Copyright © 2012 World Federation for Ultrasound in Medicine & Biology.
Published by Elsevier Inc. All rights reserved.

PMID: 22425383 [PubMed - as supplied by publisher]