title: Sustained release of bactericidal concentrations of penicillin in the pleural space via an antibiotic-eluting pigtail catheter coated with electrospun nanofibers: results from in vivo and in vitro studies.
abstract: BACKGROUND
  Inadequate intrapleural drug concentrations caused by poor penetration of systemic antibiotics into the pleural cavity is a major cause of treatment failure in empyema. Herein, we describe a novel antibiotic-eluting pigtail catheter coated with electrospun nanofibers used for the sustained release of bactericidal concentrations of penicillin in the pleural space.
  
  
  METHODS
  Electrospun nanofibers prepared using polylactide-polyglycolide copolymer and penicillin G sodium dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol were used to coat the surface of an Fr6 pigtail catheter. The in vitro patterns of drug release were tested by placing the catheter in phosphate-buffered saline. In vivo studies were performed using rabbits treated with penicillin either intrapleurally (Group 1, 20 mg delivered through the catheter) or systemically (Group 2, intramuscular injection, 10 mg/kg). Penicillin concentrations in the serum and pleural fluid were then measured and compared.
  
  
  RESULTS
  In vitro studies revealed a burst release of penicillin (10% of the total dose) occurring in the first 24 hours, followed by a sustained release in the subsequent 30 days. Intrapleural drug levels were significantly higher in Group 1 than in Group 2 (P<0.001). In the former, penicillin concentrations remained above the minimum inhibitory concentration breakpoint throughout the entire study period. In contrast, serum penicillin levels were significantly higher in Group 2 than in Group 1 (P<0.001). Notably, all Group 2 rabbits showed signs of systemic toxicity (paralytic ileus and weight loss).
  
  
  CONCLUSIONS
  We conclude that our antibiotic-eluting catheter may serve as a novel therapeutic option to treat empyema.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yin-Kai
authors.initials: YK
authors.lastname: Chao
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Cheng-Hung
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Kuo-Sheng
authors.initials: KS
authors.lastname: Liu
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Taoyuan, 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, Taoyuan, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D057785:Catheters; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019344:Lactic Acid / Q000737:chemistry; D057139:Nanofibers; D010406:Penicillins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D035422:Pleural Cavity; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020005:Propanols / Q000737:chemistry; D011817:Rabbits; D006845:Hydrocarbons, Fluorinated
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D019344:Lactic Acid; D010406:Penicillins; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020005:Propanols; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated
keywords: drug-eluting catheter; nanofibers; penicillin; pleural drainage; pleural space infections; sustained release