Low Intensity Ultrasound Mediated Liposomal XXXX Delivery Using Polymer Microbubbles.

@entity632 @entity137 @entity189 @entity3105 @entity1370
UNASSIGNED: @entity1370 is the major dose-limiting factor in the chemotherapeutic use of @entity632 ( @entity3105 ). A delivery vehicle that can be triggered to release its payload in the tumoral microvasculature but not in healthy tissue would help improve the therapeutic window of the drug. Delivery strategies combining liposomal encapsulated @entity3105 (LDox), microbubbles (MBs), and ultrasound (US) have been shown to improve therapeutic efficacy of LDox, but much remains to be known about the mechanisms and the US conditions that maximize @entity137 using this approach. In this study, we compared different US pulses in terms of drug release and acute @entity137 . Drug uptake and proliferation rates using low-intensity US were measured in squamous cell @entity189 cells exposed to LDox conjugated to or coinjected with polymer MBs. The aims of this study were: (1) to compare the effects of low- and high-pressure US on @entity3105 release kinetics; (2) to evaluate whether conjugating the liposome to the MB surface (DoxLPX) is an important factor for drug release and @entity137 ; and (3) to determine which US parameters most inhibit cell proliferation and whether this inhibition is mediated by drug release or the MB/US interaction with cells. Low-pressure US (170 kPa) at high duty cycle (stable cavitation) released up to    70% of the encapsulated @entity3105 from the DoxLPX, thus improving @entity3105 bioavailability and cellular uptake and leading to a significant reduction in cell proliferation at 48 h. Flow cytometry showed that US generating stable oscillations of DoxLPX significantly increased cellular @entity3105 uptake at 4 h after US exposure compared to LDox. Drug uptake was correlated with @entity137 at 48 h. Our results demonstrate that @entity3105 -containing liposomes conjugated to polymer MBs can be triggered to release    70% of their payload using noninertial US. Following release, @entity3105 became bioavailable to the cells and induced significantly higher @entity137 compared to nonreleased encapsulated drug. Our findings show promise for targeted drug delivery using this theranostic delivery platform at low US intensities.
