Extended pain relief achieved by analgesic-eluting biodegradable nanofibers in the Nuss procedure: in vitro and in vivo studies

Kuo-Sheng Liu,1 Wei-Hsun Chen,1 Cheng-Hung Lee,2 Yong-Fong Su,3 Shih-Jung Liu3,4 1Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, Republic of China; 2Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, Republic of China; 3Department of Mechanical Engineering, Chang Gung University, Taoyuan, Taiwan, Republic of China; 4Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, Republic of China Background: The most common complaint after the Nuss procedure is severe postoperative chest pain. The aim of this study was to evaluate the effectiveness of analgesic-eluting biodegradable nanofibers in pain relief after the Nuss procedure.Materials and methods: Poly(D,L)-lactide-co-glycolide, lidocaine, and ketorolac were dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. This solution was electrospun into a nanofibrous membrane. The elution method and high-performance chromatography were used to characterize the in vitro drug release. Stainless steel bars with and without coating of the analgesic-eluting nanofibrous membrane were implanted underneath the sternums of New Zealand white rabbits. The in vivo characteristics were further investigated.Results: The in vitro study showed that the biodegradable nanofibers released high doses of lidocaine and ketorolac within 10 days. The in vivo study demonstrated high local and systemic concentrations of lidocaine and ketorolac. The serum creatinine level was unaffected. Animals that received implants of the analgesic-eluting nanofiber-coated stainless steel bar exhibited significantly greater food and water ingestion and physical activity than the control group did, indicating effective pain relief.Conclusion: The proposed analgesic-eluting biodegradable nanofibers contribute to the achievement of extended pain relief after the Nuss procedure, without obvious adverse effects, in an animal model. Keywords: analgesic-eluting, nanofibers, biodegradable, pectus excavatum, Nuss procedure