Yin-Kai Chao1, Kuo-Sheng Liu2, Yi-Chuan Wang3, Yen-Lin Huang4, Shih-Jung Liu5. 1. Department of Thoracic and Cardiovascular Surgery, Chang Gung University, Tao-Yuan, Taiwan. 2. Department of Thoracic and Cardiovascular Surgery, Chang Gung University, Tao-Yuan, Taiwan; Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan. 3. Graduate Institute of Medical Mechatronics, Chang Gung University, Tao-Yuan, Taiwan. 4. Department of Pathology, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan. 5. Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan. Electronic address: shihjung@mail.cgu.edu.tw.
Abstract
BACKGROUND: Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems. METHODS: Biodegradable stents made of polycaprolactone were fabricated by a laboratory-made, microinjection molding machine. In vitro mechanical strength of the stents was compared with the strength of Ultraflex SEMSs. Polylactide-polyglycolide copolymer and cisplatin were coated onto the surfaces of the stents. Elution method and high-performance liquid chromatography (HPLC) analysis were used to examine the in vitro cisplatin release characteristics. In vivo, the stents were surgically implanted into the cervical trachea of 15 New Zealand white rabbits. Bronchoscopic examination was performed weekly (1 to approximately 5 weeks) before killing. Cisplatin concentrations in trachea, lung, and blood were analyzed by HPLC. Histologic examination was also performed. RESULTS: The biodegradable stent exhibited mechanical strength comparable to the strength of Ultraflex SEMSs and provided a steady release of cisplatin for >4 weeks in vitro. The in vivo study showed sustained cisplatin levels in rabbit trachea for >5 weeks with a minimum drug level in blood. Histologic examination showed an intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area. CONCLUSIONS: Our study demonstrated that the biodegradable stents provided physical properties comparable to the properties of SEMSs and a sustained release of cisplatin for >5 weeks, which showed great potential in the treatment of malignant airway obstruction.
BACKGROUND: Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems. METHODS: Biodegradable stents made of polycaprolactone were fabricated by a laboratory-made, microinjection molding machine. In vitro mechanical strength of the stents was compared with the strength of Ultraflex SEMSs. Polylactide-polyglycolide copolymer and cisplatin were coated onto the surfaces of the stents. Elution method and high-performance liquid chromatography (HPLC) analysis were used to examine the in vitro cisplatin release characteristics. In vivo, the stents were surgically implanted into the cervical trachea of 15 New Zealand white rabbits. Bronchoscopic examination was performed weekly (1 to approximately 5 weeks) before killing. Cisplatin concentrations in trachea, lung, and blood were analyzed by HPLC. Histologic examination was also performed. RESULTS: The biodegradable stent exhibited mechanical strength comparable to the strength of Ultraflex SEMSs and provided a steady release of cisplatin for >4 weeks in vitro. The in vivo study showed sustained cisplatin levels in rabbit trachea for >5 weeks with a minimum drug level in blood. Histologic examination showed an intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area. CONCLUSIONS: Our study demonstrated that the biodegradable stents provided physical properties comparable to the properties of SEMSs and a sustained release of cisplatin for >5 weeks, which showed great potential in the treatment of malignant airway obstruction.
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