You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II1 Apr 2016MP61-18 A NOVEL FORMULATION OF DOCETAXEL WITH ACTIVITY IN MUSCLE INVASIVE BLADDER CANCER XENOGRAFTS Clement Mugabe, Richard Liggins, Igor Moskalev, Michael Parr, Jayachandran Kizhakkedathu, Don Brooks, Helen Burt, and Alan So Clement MugabeClement Mugabe More articles by this author , Richard LigginsRichard Liggins More articles by this author , Igor MoskalevIgor Moskalev More articles by this author , Michael ParrMichael Parr More articles by this author , Jayachandran KizhakkedathuJayachandran Kizhakkedathu More articles by this author , Don BrooksDon Brooks More articles by this author , Helen BurtHelen Burt More articles by this author , and Alan SoAlan So More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.892AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bladder cancer is a significant public health problem responsible for more than 130,000 deaths annually word-wide. Approximately, 70-80% of patients initially present with non-muscle invasive bladder cancer (NMIBC). The rate of recurrence of NMIBC, after standard of care surgery followed by locally administered chemotherapy (mitomycin C, MMC) is 55%. Overall, 30% of patients will ultimately progress toward muscle invasive disease, which is terminal unless treated by radical cystectomy. We have developed a functionalized nanoparticle formulation of docetaxel to improve treatment outcomes of intravesical chemotherapy. Based on hyperbranched polyglycerol (HPG) technology, our new formulation (DTX/HPG-NH2): a) solubilises the drug without micelle forming surfactants which limit drug bioavailability in the bladder, b) is mucoadhesive, to prolong drug residence time after bladder voiding, c) enhances drug uptake into the bladder wall d) has demonstrated safety in preclinical models, and e) has shown promising efficacy in treating non-muscle invasive bladder tumors in mouse xenograft models. The objective of this study was to investigate the effectiveness of docetaxel formulations in a new mouse model of muscle invasive bladder cancer. METHODS Female nude mice were inoculated with UM-UC3-luc using ultrasound-guided intramural injection and tumor growth was measured by bioluminescence imaging twice a week. On day 8 post-tumor inoculation, mice with established muscle invasive bladder tumors were grouped into 3 treatment groups and were instilled with 50 µL of PBS (control), or 50 µg of docetaxel in Polysorbate 80 (Taxotere®), or 50 µg of docetaxel formulated in HPG-NH2 nanoparticles. RESULTS All mice developed bladder tumors and the success of tumor implantation was confirmed by bioluminescence and ultrasound imaging. Intravesical therapy with docetaxel HPG-NH2 formulation significantly (p<0.001, two-way ANOVA, Bonferroni post-hoc test) inhibited tumor growth compared to the Taxotere® treatment group. There was no significant difference between the Taxotere® treated group and the PBS control group. All subjects tolerated the treatments with no signs of toxicity observed in either group. CONCLUSIONS A novel formulation of docetaxel based on the HPG technology was found to be safe and effective when given intravesically to treat muscle invasive tumors in mice. To our knowledge, this is a first report on intravesical therapy for muscle invasive bladder tumor. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e810 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Clement Mugabe More articles by this author Richard Liggins More articles by this author Igor Moskalev More articles by this author Michael Parr More articles by this author Jayachandran Kizhakkedathu More articles by this author Don Brooks More articles by this author Helen Burt More articles by this author Alan So More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...