Application of biodegradable ureteral stents as delivery vehicles for anti-cancer drugs in the treatment of upper urinary tract urothelial carcinoma

Drug eluting stents can release locally pharmaceutical active ingredients, particularly in the ureter and bladder, increasing the bioavailability and efficacy of the drugs. Although drug eluting stents has been widely used and commercially available in other fields, such as cardiology, its role in urology is limited. In his work, we propose the production of biodegradable stents using a simple technology, developed and patented by the team as drug new drug delivery devices, namely for the delivery of anti-cancer drugs for the treatment of upper urinary tract urothelial carcinoma. The results of this work suggest that the viability of the cancer cells is reduced by 75% after three days of implantation while the non-cancer cells are not affected.

This work was supported by the Jaba Recordati Urology Investigation Grant 2015, awarded by the Portuguese Association of Urology. 

Authors and Affiliations:

Alexandre A. Barros^{a, b, c}, Shane Browne^{c, d}, Carlos Oliveira^{b, e}, Estevão Lima^{b, e}, Ana Rita C. Duarte^{a, b,} Kevin E. Healy^c, Rui L. Reis^{a, b}

^a 3B's Research Group—Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark—Parque de Ciência e Tecnologia, 4805-017 Barco GMR, Portugal

^b ICVS/3B’s-PT Government Associate Laboratory, Braga, Guimarães, Portugal

^c Departments of Bioengineering and Materials Science and Engineering, University of California, Berkeley, CA 94720, USA

^d Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Ireland

^e Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

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 mg drug/mg polymer: 2% loaded), while the lowest amount was obtained for paclitaxel (0.067 mg 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.

Journal: International Journal of Pharmaceutics

Link: http://www.sciencedirect.com/science/article/pii/S037851731630816X