Chairman, Dept of Urology RAMBAM HealthCare Campus
Introduction: The usual treatment for bladder tumors after local resection is instillation of chemotherapy or immunological treatment. These treatments are challenging due to short exposure time or dilution by urine production. We have developed a biodegradable device that gradually releases cisplatin into the urinary tract, to eliminate cancer cells. The device is lodged in the renal pelvis, as an alternative strategy for injecting substances into the bladder.
Methods: Using PLGA-produced poly-lactic-glycolic-acid nanofibres, we were able to trap within the polymer matrix the cisplatin that would be released into the urine stream with the gradual breakdown of the device. We tested our ability to build a device that would sit in the renal pelvis, the amount of cisplatin that could be loaded on the device, the rate of release of cisplatin at different concentrations, and the response of different TCC cell lines to exposure to cisplatin released from the disintegrated device.
Results: The device was built in the shape of KORIGAMI for maximizing its’ surface area. Cisplatin was imprinted in various concentrations (1.17-2.34% w / w). In a bioreactor that simulates artificial urine interaction with the device, a cisplatin release rate of 26% of its contents within the first 6 hours and a release of 94% of the contents after a week at a flow rate of 30 ml / hour was demonstrated. The stent completely disintegrated within 4 weeks. Two TCC cell-lines were tested (T24 & NTB9) and apoptosis was demonstrated within a few hours at all concentrations tested.
Conclusions: We attempted to build a nanofiber model as a reservoir for active substances trapped in a polymer, that decomposes under urinary flow conditions. We developed a stent that releases at a predetermined rate, a drug for a period of about several weeks. We started with cisplatin, the most effective chemotherapy in the treatment of bladder cancer. We anticipate that the location of the device in the renal pelvis it will reduce bladder irritation of existing stents. We are planned to implant the device in the renal pelvis of a swine model. We believe that a device that allows for long-term controlled release will provide a significant advantage over existing bladder cancer treatments that require multiple instillations.
Source of Funding: KAMIN Grant, Israel Ministry of Science