W. Lim, G.M. Xiong, T.W. Chong, Y. Huang, S. Venkatraman
Nanyang Technological University,
Keywords: hydrogel, ureteral stent, drug delivery, controlled release
Summary:The current methods of treating ureteric diseases such as strictures and carcinoma include endoscopic full-thickness incision of the ureteric wall and placement of an indwelling stent for up to 6 weeks. However, such interventions are not always successful, have high rates of obstruction recurrence, and require repeated interventions. It has been reported that postoperative administration of adjuvant topical drugs can reduce recurrence of ureteric disease. However, the challenge remains to achieve efficacious drug concentration in the target tissue. Current indwelling stents serve only as passive internal scaffolds and do not address any pathology e.g. fibrosis, infection, tumours. The devised technology relates to a drug-eluting ureteric stent that delivers the therapeutic agent into the diseased ureteric tissues via an expandable hydrogel coating. Drug diffusion and transport into the ureteric tissue is enhanced as the hydrogel swells and contacts with the ureteric wall. The technology comprises of the first layer of drug-eluting biodegradable polymer coating on a modified stent surface, and a second layer of expandable polyethylene (glycol) diacrylate (PEGDA) hydrogel which swells as it absorbs urine. The expandable hydrogel was demonstrated to be able to expand up to 30 times its original mass to approximately 4.5 – 5.5 mm in diameter (common ureteric diameter in adults), enabling the localized delivery of drug into the lowly permeable targeted ureteric tissues. In-vitro drug release studies with mitomycin C (MMC), a model drug used frequently in clinical practice, have demonstrated that drug release can be sustained for a period of 1 month and more (common indwelling stenting duration). The release profiles of MMC were tunable by varying the polymer coating thickness drug loading in the polymer. Using an in vitro dynamic model that simulates physiological urine flow, MMC release from the polymer coating was shown to be enhanced by the hydrogel. A working prototype of the drug-eluting stent has been fabricated and successfully tested for insertion and removability in pigs. There is currently no drug eluting ureteric stent or localized drug therapy for ureteric diseases on the market. This novel swellable hydrogel coating technology is clinically relevant for the treatment of ureteric diseases that currently have no good chemotherapeutic solutions due to the difficulty in delivering drugs into the ureteric tissues. Ureteric stent placement is very commonly practiced as an adjunct to endoscopic surgery, and treatment can be easily terminated by removal of the stent. Its value proposition lies in its compatibility for use with any commercially available ureteric stents, and by providing a unique platform to deliver therapeutic agents directly into the ureteric wall in a sustained manner. Clinicians will find this technology easy to incorporate into their practice.