Inhibition of Ureteral Stricture by Pirfenidone-Loaded Nanoparticle-Coated Ureteral Stents with Slow-Release Pirfenidone

Introduction: Ureteral stricture caused by iatrogenic ureteral injury induced ureteral injury is more common and challenging to recover quickly. The effective prevention of ureteral stricture due to iatrogenic ureteral injury-induced ureteral damage is a current challenge for urologists. The purpose of this study was to evaluate the effectiveness of nanoparticle/pirfenidone complex-coated ureteral stents with slow-release pirfenidone for the prevention of ureteral stricture in rabbits. In this study, we developed a nanoparticle/pirfenidone complex-coated ureteral stent to deliver pirfenidone into the injured ureter to inhibit ureteral stricture. Methods: Twelve New Zealand rabbits were divided into four groups: Sham, US, US+ Unmodified ureteral stent, and US+NP/PFD ureteral stent; we constructed an irreversible electroporation model of ureteral injury in rabbits and placed unmodified ureteral stents and nanoparticle/pirfenidone complex-coated ureteral stents into the ureter. Two weeks later, we euthanized the rabbits and removed their bilateral kidneys and ureters. We evaluated the effect of ureteral stent prophylaxis by gross specimen observation, section staining, and Western Blot. Results: We found that the nanoparticle/pirfenidone complexes could adhere uniformly to the surface of the ureteral stent. After placement into the ureter, the nanoparticle/pirfenidone complexes were able to remain on the surface of the ureteral stent. We found nanoparticle/pirfenidone complexes could diffuse in the ureteral epithelial tissue two weeks after the order. The study showed that nanoparticle/pirfenidone complex-coated ureteral stents placed into the ureter showed significantly less stenosis due to fibrosis than in US control rabbits and rabbits treated with unmodified ureteral stents. Conclusion: We used a novel platform based on nanoparticle/pirfenidone complex-coated ureteral stents for local and sustained delivery of pirfenidone, which can effectively deliver pirfenidone to the tissue and can slowly control the release of pirfenidone. Therefore, combining ureteral stents with nanoparticle/pirfenidone complexes was an effective measure to prevent ureteral stricture.