Drug-releasing intravesical floating technology (DRIFT) for administration of sequential gemcitabine and docetaxel in non-muscle-invasive bladder cancer.

Abstract

784 Background: Sequential intravesical gemcitabine and docetaxel (Gem/Doce) is a well-tolerated, efficacious option in a variety of settings for non-muscle invasive bladder cancer (NMIBC). This is widely utilized but nevertheless limited by logistics. We developed the Drug-Releasing Intravesical Floating Technology (DRIFT) to optimize Gem/Doce administration, enabling patient mobility and self-removal. Methods: The DRIFT device comprises a 3D-printed tube encased in a latex balloon, capped with a dissolvable polyvinyl acetate/polyvinylpyrrolidone endcap coated in Fluoropel, and a silicone endcap with a suture for patient removal. Device fabrication involved 3D printing, latex molding, and polymer coating. The procedure involves instilling intravesical gemcitabine through a 14-French catheter, followed by insertion of the deflated DRIFT device, which is then inflated with docetaxel and air to ensure buoyancy. After catheter removal, gemcitabine dwells temporarily and is subsequently voided, while the DRIFT device remains in the bladder, releasing docetaxel in a controlled, delayed fashion. Device performance was assessed in Merino sheep, dissolution kinetics were evaluated using methylene blue, and docetaxel tissue penetration was analyzed in rabbit bladder tissue using HPLC. Results: The DRIFT device enabled controlled, timed release of drug surrogate, with dissolution time of endcaps significantly prolonged by additional Fluoropel coatings as seen from 0 to 3 coatings (p < 0.0001). The device’s drug-release kinetics were evaluated by varying the inserted volume of methylene blue dye solution, used here as a drug analog. The time required for full dye release after cap dissolution significantly decreased when increasing the inserted volume from 1.5 mL to 2.0 mL (p = 0.03) and further to 3.0 mL (p = 0.003), indicating rapid dispersion and release capability at higher volumes. Volumes between 2.0 and 3.0 mL showed no significant differences, suggesting a plateau in release kinetics. In vivo, the device demonstrated reliable timed release and complete bladder dispersion of the surrogate in sheep, with retention until evacuation. Escalating gemcitabine pre-treatment concentrations enhanced subsequent docetaxel tissue penetration, with peak concentrations reaching 0.45 mg/mL versus 0.08 mg/mL with no pre-treatment. Extended gemcitabine pre-treatment dwell time further improved subsequent docetaxel delivery, achieving significant enhancement in deep tissue penetration (p = 0.0002). Conclusions: DRIFT enables controlled sequential delivery of Gem/Doce, reliably maintaining docetaxel containment for up to 120 minutes during gemcitabine pre-treatment. Future in vivo validation will establish safety and therapeutic potential.