title: Biodegradable drug-eluting pellets provide steady and sustainable cisplatin release in the intrapleural cavity: in vivo and in vitro studies.
abstract: The purpose of this study is to develop biodegradable drug-eluting pellets to provide a sustainable delivery of cisplatin intrapleurally. Poly(d,l)-lactide-co-glycolide (PLGA) (LA:GA=50:50) copolymer and cisplatin were mixed, compressed, and sintered to construct biodegradable pellets and placed in phosphate-buffered saline to test the characteristics of in vitro release. In vivo, equal amounts of cisplatin (10mg/kg) were introduced into rabbit pleural cavities either by free form (Gr1) or pellets form (Gr2). Cisplatin concentrations in the collected pleural effusion and blood were measured and compared by repeated measurement ANOVA. In vitro, approximately 5% of the cisplatin was released in the first day while the rest was gradually released in the following 50 days. In vivo, the cisplatin level in the pleural fluid was equally high during the first 2 days but dropped quickly in Gr1 while remaining high in Gr2 for 18 days, the difference was statistically significant (P<0.001) In contrast, the plasma cisplatin level was 10 times significantly higher in Gr1 than in Gr2 (P<0.001), which resulted in two early deaths of rabbits. Thus we concluded that our biodegradable pellets could achieve high and steady cisplatin release in the pleural cavity. This novel drug delivery system may have the potential to serve as an adjuvant treatment for malignant pleural lesion.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yin-Kai
authors.initials: YK
authors.lastname: Chao
authors.affiliation: Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Wen
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Kuo-Sheng
authors.initials: KS
authors.lastname: Liu
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004343:Drug Implants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D035422:Pleural Cavity / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D002945:Cisplatin
keywords: Biodegradable drug-eluting pellets; Cisplatin; Intrapleural chemotherapy; Malignant pleural effusion