A swellable drug eluting stent to target fibrosis-induced ureteral stricture

Abstract

Event Abstract Back to Event A swellable drug eluting stent to target fibrosis-induced ureteral stricture Huang Yingying1, Lim Wei Shan1, Chong Tsung Wen2, Kenneth Chen2* and Subbu Venkatraman1* 1 Nanyang Technological University, School of Materials Science and Engineering, Singapore 2 Singapore General Hospital, Urology Centre, Singapore Ureteral stricture is a serious urological disease which results in the difficulty for urine to pass through the ureter space from kidney to bladder. Consequently, this can result in hydronephrosis, morbidity and loss of a functioning kidney. Ureteral stricture may result from a variety of causes, including stone passage, endoscopic urologic procedures, radiation therapy, open or laparoscopic surgery, and penetrating traumatic injuries[1]. Standard of care comprising endoscopic incision and stenting is not always successful, nor able to produce durable favourable outcomes, and normally associated with recurrent obstruction. This study reports on a swellable bilayer drug-eluting stent to be placed in the ureter post-operatively to enhance the localized delivery of an anti-fibrotic drug into the proximate disease area with sustained delivery over the period of time when the stent is left in-situ. The swellable bilayer stents were prepared by spray coating the bare polyurethane stent with a biodegradable polymer loaded with Mitomycin C (MMC), and the hydrogel is coated via in-situ crosslinking onto the biodegradable polymer that was pre-treated with oxygen plasma. Firstly, the adhesion of the hydrogel to the polymer as well as its swelling properties was evaluated. Next, the in vitro release studies of MMC from both polymer coated stent with different coating thickness and swellable coated stent were evaluated. Lastly, the effect of the released MMC from the swellable coated stent on human bladder stroma fibroblast cells was studied. The results show the adhesion of hydrogel onto the polymeric stent coating remained firm for 28 days and the bilayer coated stent can swell up to comparable ureteric diameters of 4-5 mm, as shown in Figure 1 (A – D). Moreover, the release profile may be manipulated by thickness of PLC and the drug loading, to achieve about 10% to 50% of cumulative MMC release over 28 days (Figure 2A and 2B); the hydrogel itself does not have any effect on this release profile, Figure 2C. Finally, the release of MMC from selected coated stent is able to inhibit human bladder stroma fibroblast cells in vitro as shown in Figure 3. In conclusion, a swellable coated stent developed in our work, has the ability to adhere onto the bare PU stent for 28 days, and swell up to 4-5 mm. The release of MMC from selected coated stent is able to inhibit human bladder stroma fibroblast cells in in vitro. Therefore, a swellable coated stent can have significant benefit for managing fibrosis-induced ureteral strictures.