Drug-eluting biodegradable ureteral stent: new approach for urothelial tumors of upper urinary tract cancer

Abstract

Upper urinary tract urothelial carcinoma (UTUC) accounts for 5–10% of urothelial carcinomas and is a disease that has not been widely studied as carcinoma of the bladder. To avoid the problems of conventional therapies, such as the need for frequent drug instillation due to poor drug retention, we developed a biodegradable ureteral stent (BUS) impregnated by supercritical fluid CO2 (scCO2) with the most commonly used anti-cancer drugs, namely paclitaxel, epirubicin, doxorubicin, and gemcitabine. The release kinetics of anti-cancer therapeutics from drug-eluting stents was measured in artificial urine solution (AUS). The in vitro release showed a faster release in the first 72 h for the four anti-cancer drugs, after this time a plateau was achieved and finally the stent degraded after 9 days. Regarding the amount of impregnated drugs by scCO2, gemcitabine showed the highest amount of loading (19.57 μg drug/mg polymer: 2% loaded), while the lowest amount was obtained for paclitaxel (0.067 μg drug/mg polymer: 0.01% loaded). A cancer cell line (T24) was exposed to graded concentrations (0.01–2000 ng/ml) of each drugs for 4 and 72 h to determine the sensitivities of the cells to each drug (IC50). The direct and indirect contact study of the anti-cancer biodegradable ureteral stents with the T24 and HUVEC cell lines confirmed the anti-tumoral effect of the BUS impregnated with the four anti-cancer drugs tested, reducing around 75% of the viability of the T24 cell line after 72 h and demonstrating minimal cytotoxic effect on HUVECs.