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 72h 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 (19.57μg drug/mg polymer: 2% loaded), while the lowest amount was obtained for paclitaxel (0.067μg drug/mg polymer: 0.01% loaded). A cancer cell line (T24) was exposed to graded concentrations (0.01-2000ng/ml) of each drugs for 4 and 72h 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 72h and demonstrating minimal cytotoxic effect on HUVECs.
International journal of pharmaceutics. 2016 Aug 30 [Epub ahead of print]
Alexandre A Barros, Shane Browne, Carlos Oliveira, Estevão Lima, Ana Rita C Duarte, Kevin E Healy, Rui L Reis
3B́s 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; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal; Departments of Bioengineering and Materials Science and Engineering, University of California, Berkeley, CA 94720, USA., Departments of Bioengineering and Materials Science and Engineering, University of California, Berkeley, CA 94720, USA; Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Ireland., ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal; Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal., 3B́s 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; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal. Electronic address: ., Departments of Bioengineering and Materials Science and Engineering, University of California, Berkeley, CA 94720, USA., 3B́s 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; ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.