Biodegradable cisplatin-eluting tracheal stent for malignant airway obstruction: in vivo and in vitro studies.
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.
Department of Thoracic and Cardiovascular Surgery, Chang Gung University, Tao-Yuan, Taiwan.
Yin-Kai
YK
Chao
Department of Thoracic and Cardiovascular Surgery, Chang Gung University, Tao-Yuan, Taiwan; Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
Kuo-Sheng
KS
Liu
Graduate Institute of Medical Mechatronics, Chang Gung University, Tao-Yuan, Taiwan.
Yi-Chuan
YC
Wang
Department of Pathology, Chang Gung Memorial Hospital, Linkou, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Yen-Lin
YL
Huang
Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan. Electronic address: shihjung@mail.cgu.edu.tw.
Shih-Jung
SJ
Liu
D020341:Absorbable Implants / Q000592:standards*; D000402:Airway Obstruction / Q000209:etiology / Q000628:therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000627:therapeutic use; D002945:Cisplatin / Q000097:blood / Q000627:therapeutic use*; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents / Q000592:standards*; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy*; D008422:Materials Testing; D010166:Palliative Care; D011817:Rabbits; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D002945:Cisplatin