In vitro and ex-vivo permeability studies of paclitaxel and doxorubicin from drug-eluting biodegradable ureteral stents

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 (IDD) system. BUS has revealed to reduce in 75% the viability of human urothelial cancer cells (T24) after 72 h of contact and demonstrated the 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 paclitaxel, and doxorubicin, alone or released from the BUS developed. We used three different membranes to study the permeability: polyethersulphone membrane (PES), HUVECs cell monolayer and an ex vivo porcine ureter. The ureter thickness was measured (864.51 μm) and histological analysis was performed to confirmed the integrity of urothelium. Permeability profiles were measured during 8 hours, 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, being the PES more permeable and the ex vivo ureter tissue 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 (Kd) 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 remains in the ex vivo ureter tissue shown to be effective to affect the cancer cell and did not affect the non-cancer cells.