Evaluation of Loading Strategies to Improve Tumor Uptake of Gemcitabine in a Murine Orthotopic Bladder Cancer Model Using Ultrasound and Microbubbles

In this study we compared three different microbubble-based approaches to the delivery of a widely used chemotherapy drug, gemcitabine: (i) co-administration gemcitabine and microbubbles (Gem+MB); (ii) conjugates gemcitabine-loaded liposomes (GemlipoMB); (iii) with directly bound their surfaces (GembioMB). Both in vitro vivo investigations were carried out, respectively, RT112 bladder cancer cell line murine orthotopic muscle-invasive model. The (in vivo) ultrasound exposure conditions 1 (1.1) MHz centre frequency, 0.07 (1.0) MPa peak negative pressure, 3000 (20,000) cycles 100 (0.5) Hz pulse repetition frequency. Ultrasound produced no significant increase drug uptake either or drug-only control for co-administered microbubbles. vivo, GemlipoMB prolonged plasma circulation time gemcitabine, but only GembioMB statistically cleaved caspase 3 expression tumor, indicative gemcitabine-induced apoptosis.