Animal model assessment of a new design for a coated mitomycin-eluting biodegradable ureteral stent for intracavitary instillation as an adjuvant therapy in upper urothelial carcinoma.

BACKGROUND: A major limitation in the treatment of upper urinary tract urothelial carcinoma is the limited use of adjuvant therapy due to the drawbacks of current techniques for intracavitary instillation. The aim was to assess, in a large animal model, a biodegradable ureteral stent coated with silk fibroin for mitomycin release, i.e. BraidStent-SF-MMC. METHODS: A total of 14 female pigs with a solitary kidney underwent initial urinalysis, blood chemistry, nephrosonographic, and contrast fluoroscopy assessment of the urinary tract. Later, the BraidStent-SF-MMC was placed retrogradely to assess the mitomycin urine concentration from 0-48 hours. Follow-up was performed weekly until complete stent degradation to assess the macroscopic and microscopic changes in the urinary tract, stent complications. RESULTS: The drug eluting stent released mitomycin for the first 12 h. The main complication was the release of obstructive ureteral coating fragments during the first to third week in 28.5 and 7.1% of animals, respectively, related to urinary pH<7.0, which destabilized the stent coating. Another complication was ureteral strictures between the fourth and sixth week in 21%. The stents were completely degraded by 6-7 weeks. There were no stent-related systemic toxic effects. The success rate was 67.5% and the complication rate was 25.7%. CONCLUSIONS: For the first time, we have shown that a biodegradable anti-cancer drug eluting stent, BraidStent-SF-MMC, provides controlled and well-tolerated release of mitomycin into the upper urinary tract in an animal model. Mitomycin release from a silk fibroin coating could be a compelling approach for adjuvant chemotherapy instillation in upper tract urothelial carcinoma management.

Cytotoxicity Assessment of a New Design for a Biodegradable Ureteral Mitomycin Drug-Eluting Stent in Urothelial Carcinoma Cell Culture.

Urothelial tumour of the upper urinary tract is a rare neoplasm, but unfortunately, it has a high recurrence rate. The reduction of these tumour recurrences could be achieved by the intracavitary instillation of adjuvant chemotherapy after nephron-sparing treatment in selected patients, but current instillation methods are ineffective. Therefore, the aim of this in vitro study is to evaluate the cytotoxic capacity of a new instillation technology through a biodegradable ureteral stent/scaffold coated with a silk fibroin matrix for the controlled release of mitomycin C as an anti-cancer drug. Through a comparative study, we assessed, in urothelial carcinoma cells in a human cancer T24 cell culture for 3 and 6 h, the cytotoxic capacity of mitomycin C by viability assay using the CCK-8 test (Cell counting Kit-8). Cell viability studies in the urothelial carcinoma cell line confirm that mitomycin C embedded in the polymeric matrix does not alter its cytotoxic properties and causes a significant decrease in cell viability at 6 h versus in the control groups. These findings have a clear biomedical application and could be of great use to decrease the recurrence rate in patients with upper tract urothelial carcinomas by increasing the dwell time of anti-cancer drugs.

Biodegradable ureteral stents: in vitro assessment of the degradation rates of braided synthetic polymers and copolymers.

OBJECTIVES: The control and predictability of degradation rates and the absence of obstructive phenomena are two main challenges for research regarding biodegradable ureteral stents. The objectives are to assess the degradation performance and safety of braided combinations of three synthetic biodegradable polymers and copolymers; and to evaluate the interference of a heparin dip coating on degradation and bacterial colonization. METHODS: The hydrolysis of polyglycolic acid (PGA), poly lactic-co-glycolic acid (PLGA) and Glycomer™ 631 is assessed in this in vitro study that comprises ten groups. Stent samples present a braided arrangement and are incubated in porcine urine that undergoes analysis and exchange every 48 h until degradation. Coating is carried out with sodium heparin via dip coating and determination of the heparin release is carried out by ELISA test. Variables of study are stent mass, mass fold change, degradation time, bacterial colonization and concentration of heparin released in artificial urine. RESULTS: There is statistical significance in degradation times between all materials except between the Glycomer™ 631 alone and combined with PGA. Mass fold change analysis of the Glycomer™ 631 evidences an increasing trend of its mass during degradation. The combination of Glycomer™ 631 and PGA presents a progressive and gradual degradation, where PGA degrades at week 3 while Glycomer™ 631 remains intact until its fragmentation at the late stage of degradation. Heparin coating has no significant impact on mean degradation times and trends in any group, nor on bacteriuria rates; heparin concentration decreases significantly after 72 h. Products of degradation are released steadily with minimum dimensions. CONCLUSIONS: The combination of synthetic biodegradable polymers and copolymers with different degradation rates provides a gradual staged degradation. Heparin dip coating is a safe and feasible technique to coat biodegradable ureteral stents without interfering in degradation rates although it does not have a significant effect on the onset of bacterial colonization.