316 SUCCESSFUL INTRAVESICAL THERAPY FOR BLADDER CANCER UTILIZING PACLITAXEL CONTAINING NANOPARTICLES

Abstract

You have accessJournal of UrologyUrothelial Cancer: Medical & Surgical Therapy1 Apr 2010316 SUCCESSFUL INTRAVESICAL THERAPY FOR BLADDER CANCER UTILIZING PACLITAXEL CONTAINING NANOPARTICLES Mary Samplaski, Armine Smith, William Larchian, Vinod Labhasetwar, and Warren Heston Mary SamplaskiMary Samplaski More articles by this author , Armine SmithArmine Smith More articles by this author , William LarchianWilliam Larchian More articles by this author , Vinod LabhasetwarVinod Labhasetwar More articles by this author , and Warren HestonWarren Heston More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.380AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES About 70% of bladder cancers are superficial and amenable to intravesical therapy. Nanoparticles (NPs) provide a vehicle for localized drug delivery. They achieve rapid intracellular penetration and provide slow, regional release of encapsulated drug. The transferrin receptor (TfR) is overexpressed in bladder cancer cells. Paclitaxel (Tx) has activity against human bladder cancer. To optimize NP preparation, we evaluated Tf and poly-L-lysine (PLL) conjugated NP penetration. We then tested Tf conjugated NPs for Tx delivery to bladder cancer cells in a murine model. METHODS After bladder pretreatment with PLL, orthotopic MBT-2 bladder tumors were induced in C3H/HeJ female mice. Tumors were confirmed sonographically at 14 days. Coumarin-conjugated NPs were instilled intravesically in several groups: with & without PLL pretreatment, conjugated & unconjugated to PLL, and conjugated & unconjugated to Tf. Confocal microscopy of bladders was done after 1.5 hours of incubation. All subsequent experiments used Tf-conjugated NPs without PLL pretreatment. Cremophor (solvent for Tx) & Tx, Cremophor & saline, saline, and Tx loaded NPs (8 mg/kg) were instilled intravesically for 1.5 hours. Ultrasound was performed starting on post-instillation day (PID) 5. Bladders were examined on PID 15. RESULTS Tf conjugation led to enhanced NP accumulation in the tumors. PLL conjugation and PLL pre-wash enhanced overall penetration but negated the selective tumor binding. By PID 5 the Cremophor, Cremophor & saline, and saline groups had developed enlarging bladder tumors > 1mm. On PID 5 and 7, tumors in the Tx-NP group were comparatively smaller, 0.682mm and 0.878mm, respectively. By PID 9 tumors in the Tx-NP group were also enlarging (Fig 1). Histolology confirmed invasive tumors in all groups on PID 15. CONCLUSIONS Tf-NP conjugation allows for selective uptake of the NP by cancer cells. A single dose of NP encapsulated Tx suppresses murine superficial bladder tumor growth for 7 days. Further studies will focus on repeated dosing of Tx-NPs and increasing the dose of Tx. Cleveland, OH© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e125 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mary Samplaski More articles by this author Armine Smith More articles by this author William Larchian More articles by this author Vinod Labhasetwar More articles by this author Warren Heston More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...