School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore; Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR), 2 Fusionopolis Way Innovis, Singapore, 138634, Singapore; Sino-Singapore International Joint Research Institute, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.
Department of Urology, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore.
Biomaterials. 2018 May;165:25-38. doi: 10.1016/j.biomaterials.2018.02.035. Epub 2018 Feb 20.
A bilayer swellable drug-eluting ureteric stent (BSDEUS) is engineered and implemented, as a sustained drug delivery platform technology that enhances localized drug delivery to the highly impermeable urothelium, for the treatment of urothelial diseases such as strictures and carcinomas. On deployment, the device swells to co-apt with the ureteric wall and ensure drug availability to these tissues. BSDEUS consists of a stent spray-coated with a polymeric drug containing polylactic acid-co-caprolactone (PLC) layer which is overlaid by a swellable polyethylene glycol diacrylate (PEGDA) based hydrogel. In-vitro quantification of released drug demonstrated a tunable time-profile, indicating sustained delivery over 1-month. The PEGDA hydrogel overlayer enhanced drug release and transport into explanted porcine ureteric tissues ex-vivo, under a simulated dynamic fluid flow. A preliminary pilot in-vivo feasibility study, in a porcine model, demonstrated that the swollen hydrogel co-apts with the urothelium and thus enables localized drug delivery to the target tissue section. Kidney functions remained unaffected and device did not result in either hydronephrosis or systemic toxicity. This successful engineering of a bilayer coated stent prototype, demonstrates its feasibility, thus offering a unique solution for drug-based urological therapy.
双层可膨胀药物洗脱输尿管支架(BSDEUS)被设计和实现,作为一种持续的药物输送平台技术,增强了对高度不可渗透的尿路上皮的局部药物输送,用于治疗尿路上皮疾病,如狭窄和癌。在部署时,该设备会膨胀以与输尿管壁配合,并确保药物可用于这些组织。BSDEUS 由支架喷涂而成,涂有含有聚乳酸-己内酯(PLC)的聚合物药物层,上面覆盖有可膨胀的聚乙二醇二丙烯酸酯(PEGDA)基水凝胶。体外释放药物的定量分析表明,可调节的时间曲线表明可在 1 个月以上持续释放。PEGDA 水凝胶覆盖层增强了药物释放和运输到离体猪输尿管组织中,在模拟动态流体流动下。在猪模型中的初步初步体内可行性研究表明,膨胀的水凝胶与尿路上皮共配合,从而能够将药物局部输送到目标组织部分。肾功能保持不变,且设备不会导致肾积水或全身毒性。这种双层涂层支架原型的成功工程设计证明了其可行性,为基于药物的泌尿科治疗提供了独特的解决方案。