Drug-releasing intravesical floating technology for sequential gemcitabine and docetaxel in non-muscle-invasive bladder cancer

Abstract

Objectives: To develop a drug-releasing intravesical floating technology (DRIFT) device for controlled sequential delivery of gemcitabine and docetaxel (Gem/Doce) to optimise the treatment of non-muscle-invasive bladder cancer (NMIBC) while enabling patient mobility and self-removal, as sequential intravesical Gem/Doce has been increasingly utilised but has logistical limitations requiring prolonged clinic visits and patient immobilisation. Materials and Methods: The DRIFT device features a three-dimensional printed perforated tube with latex sleeve, dissolvable polyvinyl acetate and polyvinylpyrrolidone end cap with adjustable fluorinated polymer (FluoroPel) coating, and patient-removal suture. A 14-F catheter is placed and intravesical gemcitabine is instilled. The deflated DRIFT device is inserted via catheter and inflated with docetaxel and air. The catheter is removed, allowing gemcitabine to dwell temporarily and be voided by the patient. The DRIFT device remains in the bladder and subsequently releases docetaxel in a controlled, delayed fashion, followed by patient removal. Its flexible, buoyant design supports patient mobility and maintains unimpeded urinary flow. Dissolution kinetics were evaluated using methylene blue, device performance was assessed in Merino sheep, and docetaxel tissue penetration was evaluated in rabbit bladder tissue using high-performance liquid chromatography analysis. Results: The DRIFT device demonstrated adaptable drug release through FluoroPel coating optimisation, with dissolution times extending significantly from zero to three coatings (P < 0.001). Docetaxel release kinetics plateaued between 2.0 and 3.0 mL volumes. Sheep studies revealed similar timed drug release as in vitro testing. Escalating gemcitabine concentrations enhanced docetaxel tissue penetration, with peak concentrations reaching 0.45 vs 0.08 mg/mL in controls. Extended gemcitabine dwell time (up to 4 h) further improved docetaxel delivery, achieving significant enhancement in deep tissue penetration (P < 0.001). Conclusion: The DRIFT enables controlled sequential delivery of Gem/Doce, reliably maintaining docetaxel containment for up to 120 min during gemcitabine pre-treatment. Future in vivo validation will establish safety and therapeutic potential. This platform has broader applications beyond NMIBC, including urinary tract infections and interstitial cystitis.