Dual-layer drug release system based on ureteral stents inhibits the formation of ureteral stricture

Abstract

Ureteral stricture is a common urological condition caused by the proliferation of scar tissue at the site of the stenosis. Effectively inhibition of scar tissue proliferation at ureter is key to preventing stenosis after ureteral injury. Retention of an anti-fibrotic-loaded ureteral stent tube that gradually releases the drug can inhibit scar tissue proliferation, thus preventing and treating ureteral stricture. In this study, double layers drug release system was used to carry pirfenidone to create ureteral stent tubes for preventing ureteral stricture. Long-term sustained release of pirfenidone was assessed, and the anti-stenosis drug was continuously released by the stent, which also provided drainage support. Drug release data showed that the stent tube experiments rapidly released pirfenidone over the first 5 days, with the release becoming stable and gradual over the subsequent 9 days. In vitro data showed that the stent tube had a sustained inhibitory effect on human ureteral smooth muscle cells, a significant inhibitory effect on macrophages and an anti-inflammatory factor release effect. More importantly, in vivo data showed that the stent tube had a significant inhibitory effect on ureteral stricture formation in a model of porcine ureteral stricture. These results suggested that the proposed stent tube, a novel pirfenidone sustained-release stent, can effectively inhibit the formation and progression of ureteral stenosis in vitro and in vivo.