@article {Barros2017b,
	title = {{In~Vitro and Ex~Vivo Permeability Studies of Paclitaxel and Doxorubicin From Drug-Eluting Biodegradable Ureteral Stents}},
	journal = {Journal of Pharmaceutical Sciences},
	volume = {106},
	number = {6},
	year = {2017},
	note = {n/a},
	abstract = {<p>{\textcopyright} 2017 American Pharmacists Association{\textregistered} A drug-eluting biodegradable ureteral stent (BUS) has been developed as a new approach for the treatment of urothelial tumors of upper urinary tract cancer. In a previous work, this system has proven to be a good carrier for anticancer drugs as a potential effective and sustainable intravesical drug delivery system. BUS has revealed to reduce in 75{\%} the viability of human urothelial cancer cells (T24) after 72~h of contact and demonstrated minimal cytotoxic effect on human umbilical vein endothelial cells (HUVECs) which were used as a control. In this work, we studied the permeability of the anticancer drugs, such as paclitaxel and doxorubicin, alone or released from the BUS developed. We used 3 different membranes to study the permeability: polyethersulfone (PES) membrane, HUVECs cell monolayer, and an ex~vivo porcine ureter. The ureter thickness was measured (864.51 $μ$m) and histological analysis was performed to confirm the integrity of urothelium. Permeability profiles were measured during 8~h for paclitaxel and doxorubicin. The drugs per se have shown to have a different profile and as expected, increasing the complexity of the membrane to be permeated, the permeability decreased, with the PES being more permeable and the ex~vivo ureter tissue being less permeable. The molecular weight has also shown to influence the permeability of each drug and a higher percentage for doxorubicin (26{\%}) and lower for paclitaxel (18{\%}) was observed across the ex~vivo ureter. The permeability (P), diffusion (D), and partition (K d ) coefficients of paclitaxel and doxorubicin through the permeable membranes were calculated. Finally, we showed that paclitaxel and doxorubicin drugs released from the BUS were able to remain in the ex~vivo ureter and only a small amount of the drugs can across the different permeable membranes with a permeability of 3{\%} for paclitaxel and 11{\%} for doxorubicin. The estimated amount of paclitaxel that remains in the ex~vivo ureter tissue is shown to be effective to affect the cancer cell and not affect the noncancer cells.</p>
},
	keywords = {Biodegradable polymers, doxorubicin permeability, paclitaxel, Upper tract urothelial carcinoma, ureteral stents},
	issn = {15206017},
	doi = {10.1016/j.xphs.2017.02.023},
	author = {Barros, A.A. and Oliveira, C. and Reis, R.L. and Lima, E. and Duarte, A.R.C.}
}
