ABSTRACT
Intravesical therapy for the treatment of superficial urinary bladder tumors is promising. However, it is also challenging, due to bladder contraction and relaxation and drug elimination via urination or dilution by urine production. We developed a biodegradable drug-eluting device positioned in the renal pelvis as an alternative strategy for bladder instillation. The urine drains from the renal pelvis into the ureter, collects the eluted drug, and transports it into the bladder. The combination of the renal pelvis and the bladder creates a two-compartment system. The drug is administered into the depot compartment, the renal pelvis, and is instantly and homogeneously distributed into the central compartment, the bladder. This results in an increase in its residence time and in gradual adsorption into the urothelium. The device is inserted through the ureter, followed by upset bulging after reaching the renal pelvis in order to guarantee fixation, while preventing urinary obstruction. The device is made of electrospun poly(lactic-co-glycolic acid) (PLGA) fibers that encapsulate a chemotherapeutic drug, cisplatin (1.17-2.34% w/w). Experimental studies of the stresses developed during the bulging and simulations of the urine flow interaction with the device demonstrated structural longevity and operational safety of the device. Sustained release of 94% of the device content was demonstrated after 1 week in vitro with a flow rate of 30 mL/h. We believe that the drug-eluted device may offer a significant advantage over existing therapies for treatment of nonmuscle invasive bladder cancer.
