title: Increased accumulation and retention of micellar paclitaxel in drug-sensitive and P-glycoprotein-expressing cell lines following ultrasound exposure.
abstract: 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.
authors.affiliation: University of British Columbia, Vancouver, BC, Canada.
authors.forename: Chung Ping Leon
authors.initials: CP
authors.lastname: Wan
authors.forename: John K
authors.initials: JK
authors.lastname: Jackson
authors.forename: Fatemeh Nazly
authors.initials: FN
authors.lastname: Pirmoradi
authors.forename: Mu
authors.initials: M
authors.lastname: Chiao
authors.forename: Helen M
authors.initials: HM
authors.lastname: Burt
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D004337:Drug Carriers / Q000138:chemical synthesis*; D053672:Electrochemotherapy / Q000379:methods*; D005260:Female; D019220:High-Energy Shock Waves; D051379:Mice; D008823:Micelles; D017239:Paclitaxel / Q000493:pharmacokinetics*; D011108:Polymers / Q000138:chemical synthesis*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D017239:Paclitaxel