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

Abstract

BackgroundThe 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 methodsPoly(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.ResultsThe 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.ConclusionThe 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.

Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum

“…Lidocaine and ketorolac were employed as the analgesics. Figure 6D shows a photo of the electro-spun nanofibrous membranes, which had a thickness of approximately 0.12 mm and discharged sustained lidocaine and ketorolac for over 10 days, as shown in our previous study [22].…”

“…The degradation rate of PLGA is related to the LA:GA monomers' ratio, and the copolymer with 50:50 ratio exhibits the faster degradation (approximately 1-2 months) [19][20][21]. Our previous study incorporated analgesic-eluting nanofibers onto metallic Nuss bar and achieved the sustained and effective release of lidocaine and ketorolac for post-surgery pain relief for over 10 days (28.3 µg/mL and 17.8 µg/mL, respectively, for lidocaine and ketorolac at day 10) [22]. In addition, we used ethanol for the disinfection of PLA bars.…”

“…In this work, the analgesic-eluting nanofibers were integrated with the PLA Nuss bars. Our previous study [22] investigated the influence of metal bars on animals' activity, and found that the trigger count for metal bar implanted rabbits was 6184 ± 323. The bare PLA bar implanted animals exhibited inferior trigger counts (5512 ± 148) than the metal bar deployed animals (p < 0.05), possibly due to the greater thickness of PLA bars (PLA bar: 4.14 mm, metal bar: 3.0 mm) that induced more severe pain in the rabbit's chest cavity.…”

Development of a Biodegradable Subcutaneous Implant for Prolonged Drug Delivery Using 3D Printing

“…Interestingly, implants with 1.0 × 1.0 mm "windows" were capable of providing drug release over 25 days. A sustained release profile like this can be useful for local antimicrobial therapy or for pain management after surgery [46,47]. In these cases, a prolonged release over a period of a few weeks can be extremely beneficial to prevent infections or for pain management.…”

Lidocaine-eluting endotracheal tube effectively attenuates intubation related airway response

“…Thus, low MW PLGA are softer than common PLGA, which was well-known to be "stiff" (29,30). Several studies have reported biodegradable nanofiber membrane for the sustainable release of LDC significantly relieves the pain from surgical wounds or bone fractures in animal models (31)(32)(33). In our study, we set up the ratio of PLGA-to-LDC as a 1:1 mixture to facilitate higher amounts of LDC and more rapid drug release (33).…”