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

Yin-Kai Chao,1 Cheng-Hung Lee,2 Kuo-Sheng Liu,1 Yi-Chuan Wang,3 Chih-Wei Wang,4 Shih-Jung Liu3 1Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan; 4Department of Pathology, Chang Gung Memorial Hospital-Linkou, College of Medicine, Chang Gung University, Taoyuan, Taiwan 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).Conclusion: We conclude that our antibiotic-eluting catheter may serve as a novel therapeutic option to treat empyema. Keywords: pleural space infections, pleural drainage, drug-eluting catheter, nanofibers, penicillin, sustained release