title: 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 72h for the four anti-cancer drugs, after this time a plateau was achieved and finally the stent degraded after 9days. Regarding the amount of impregnated drugs by scCO2, gemcitabine showed the highest amount of loading (19.57μgdrug/mgpolymer:2% loaded), while the lowest amount was obtained for paclitaxel (0.067μgdrug/mgpolymer: 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.
authors: 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.
authors: Alexandre A
authors: AA
authors: Barros
authors: 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.
authors: Shane
authors: S
authors: Browne
authors: 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.
authors: Carlos
authors: C
authors: Oliveira
authors: 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.
authors: Estevão
authors: E
authors: Lima
authors: 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: aduarte@dep.uminho.pt.
authors: Ana Rita C
authors: AR
authors: Duarte
authors: Departments of Bioengineering and Materials Science and Engineering, University of California, Berkeley, CA 94720, USA.
authors: Kevin E
authors: KE
authors: Healy
authors: 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.
authors: Rui L
authors: RL
authors: Reis
mesh_terms: D020341:Absorbable Implants; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002277:Carcinoma; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D065546:Drug Liberation; D054855:Drug-Eluting Stents; D015251:Epirubicin / Q000008:administration & dosage / Q000737:chemistry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D014513:Ureter; D014556:Urine / Q000737:chemistry; D014571:Urologic Neoplasms; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D015251:Epirubicin; D004317:Doxorubicin; D017239:Paclitaxel; D000093542:Gemcitabine
keywords: Anti-cancer drugs; Biodegradable polymers; Supercritical fluid technology; T24 cell line; Upper tract urothelial carcinoma; Ureteral stents