A Nanostructured Degradable Ureteral Stent Fabricated by Electrospinning for Upper Urinary Tract Reconstruction.

A degradable polycaprolactone(PCL)/poly(lactic-co-glycolic acid, LA:GA = 80:20) (PLGA) ureter tubular stent was fabricated by electrospinning. The structure and properties of the stents were investigated by the mechanical property testing, scanning electron microscopy (SEM), degradability test in vitro and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The stent was transplanted to the dorsal muscle of rabbit to evaluate its tissue compatibility. It was shown that the stent has the nano-structure. The mechanical test showed that with the increase in PCL concentration, the mechanical properties of the stent gradually increased, and it could meet the demands of a urethral stent. The collapse time of different concentration of PCL/PLGA (5%, 15%, and 25%) was 28, 42, and 56 days, respectively. These results provide strong evidence that the degradation time can be increased with the increase in PCL concentration. The results of the MTT assay show that the PCL/PLGA stent had no cytotoxicity. In muscle implantation tests, acute tissue reactions due to operation trauma were seen in all specimens at 1 week. After four weeks, the number of inflammatory cells had decreased significantly. Only a few inflammatory cells were seen in the PCL/PLGA stent group after 12 weeks, and the foreign body reaction was more severe in the control group. Animal orthotopic transplantation experiments of these ureteral stents will be done to evaluate its degradable model and tissue compatibility.

Laden Nanofiber Capsules for Local Malignancy Chemotherapy.

In contrast to systemic chemotherapy, the local administration of chemotherapeutics potentially optimizes their accumulation in the tumor tissues and alleviates the associated systemic toxicity. However, the lack of control over the release of encapsulated drugs and their degradation represents a major challenge for local drug delivery systems. In this study, we developed a series of epirubicin (EPI)-loaded poly(ε-caprolactone)/poly(lactide-co-glycolide) (PCL/PLGA) nanofiber capsules with adjustable rates of drug release and degradation for local malignancy chemotherapy. The core-sheath PCL/PLGA nanofiber capsules containing 15.0 or 25.0 wt% of PCL in the sheath and 0, 5.0, or 10.0 wt% of EPI in the core were produced by emulsion electrospinning technology. The EPI release and degradation of the nanofiber capsules could be accelerated by decreasing the PCL content in the sheath. More importantly, the EPI-loaded PCL/PLGA nanofiber capsules effectively inhibited the growth of tumor cells in vitro and in vivo. Moreover, none of the laden nanofiber capsules caused apparent systemic toxicity. Hence, the cytostatic-loaded electrospun polyester nanofiber capsules displayed controlled drug release and degradation, along with satisfactory antitumor properties, indicating their great potential in local malignancy chemotherapy.

Gradiently degraded electrospun polyester scaffolds with cytostatic for urothelial carcinoma therapy.

Kidney-sparing surgery is the preferred treatment strategy for low-risk upper tract urothelial carcinoma (UTUC). However, after this procedure, prevention of the carcinoma recurrence in the ureter and supporting the ureter with a ureteral stent are necessary. Biodegradable drug-loaded ureteral scaffolds are able to maintain their long-term effective drug concentrations in the lesion sites without the defects of traditional ureteral stents, which may address both issues simultaneously. The purpose of this study was to reveal the possibility of the controlled delivery of epirubicin (EPI) via gradiently degraded electrospun poly(ε-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA) scaffolds to evaluate their antitumor activity against UTUC. The degradable PCL/PLGA scaffolds containing 15.0 and 25.0 wt% PCL and loading of 0, 5.0, and 10.0 wt% EPI were successfully fabricated via electrospinning. In addition, the PCL/PLGA scaffolds showed sustained and controlled degradation and drug release kinetics, that is, their degradation and drug release rates slowed with an increase in the ratio of PCL. The EPI-loaded PCL/PLGA scaffolds showed excellent antitumor activities both in vitro and in vivo without apparent systemic toxicity. Overall, the gradiently-degraded EPI-loaded electrospun polyester scaffolds are potential ureteral stent tubes for the local inhibition of the recurrence of UTUC, where the continued release of EPI can prevent the subsequent proliferation of residual tumor cells, and the gradient degradation is consistent with the repair of the ureter.

Characterization of nanostructured ureteral stent with gradient degradation in a porcine model.

A tubular poly(ε-caprolactone) (PCL)/poly(lactide-co-glycolide) (PLGA) ureteral stent composed of nanofibers with micropores was fabricated by double-needle electrospinning. The stent was ureteroscopically inserted into six Changbai pigs, and the commercial polyurethane Shagong(®) stent was inserted into four pigs as control. Intravenous pyelography revealed that the PCL/PLGA stent gradually degraded from the distal end to proximal terminal, and all stents were completely degraded at 10 weeks post-insertion. No significant difference was observed in hydronephrosis severity between the two groups. The levels of serum creatinine and urine pH remained similar throughout the study in the two groups, but the number of white blood cells in the urine was significantly higher in the Shagong(®) stent group. On Day 70, histological evaluation indicated equivalent histological severity scores in the middle and distal ureter sections and bladder in the two groups. However, the PCL/PLGA stent-implanted pigs had significantly lower mean severity scores in the kidney and proximal ureter sites. These data revealed that the PCL/PLGA stent degraded in a controlled manner, did not induce obstruction, and had a lower urothelial impact in comparison to the Shagong(®) stent, indicating that the stent exhibited great potential for clinical application.