Aplicação de cateteres ureterais biodegradáveis como veículos de libertação de fármacos para o tratamento de tumores do tracto superior do ureter

Os cateteres farmacológicos podem libertar compostos ativos que agem localmente no ureter ou bexiga aumentando assim a sua biodisponibilidade e eficiência. Embora a tecnologia com libertação de fármacos de cateteres esteja já comercialmente disponível noutros campos, tais como na cardiologia, o seu papel na urologia tem sido limitado. Neste trabalho, propusemos a criação de cateteres biodegradáveis através de uma tecnologia simples, desenvolvida pela nossa equipa e já patenteada como veículos de libertação de fármacos anti-cancerígenos para o tratamento de tumores do trato superior do ureter. Os resultados sugerem que a viabilidade das células cancerígenas em contacto com os cateteres desenvolvidos é reduzida em 75% ao fim de três dias de implante ao mesmo tempo que as células não tumorais não são afectadas.

Este trabalho foi financiado pela Bolsa de Investigação Jaba Recordati Urologia 2015, atribuída pela Associação Portuguesa de Urologia.
 

Autores e Afiliações:

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.

Revista: International Journal of Pharmaceutics

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