Electrospun fibrous membranes featuring sustained release of ibuprofen reduce adhesion and improve neurological function following lumbar laminectomy

• Published in: Journal of controlled release 2017-10, Vol.264, p.1-13
• Main Authors: Liu, Shen, Pan, Guoqing, Liu, Guangwang, Neves, José das, Song, Sa, Chen, Shuai, Cheng, Bangjun, Sun, Zhiyong, Sarmento, Bruno, Cui, Wenguo, Fan, Cunyi
• Format: Article
• Language: English
• Subjects: Acrylates - chemistry; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biodegradation; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Drug Liberation; Electrospun fibers; Epidural fibrosis; Fibrosis; Ibuprofen - administration & dosage; Ibuprofen - chemistry; Ibuprofen - therapeutic use; Laminectomy; Lumbar Vertebrae - surgery; Male; Membranes, Artificial; Microscopy, Electron, Transmission; Nerve Degeneration - drug therapy; Physical barrier; Prodrug; Rats, Sprague-Dawley; Sciatic Nerve - drug effects; Sciatic Nerve - pathology; Sciatic Nerve - physiology; Sciatic Nerve - ultrastructure; Tissue Adhesions - drug therapy
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2017.08.011

Electrospun fibrous membranes provide suitable physical anti-adhesion barriers for reducing tissue anti-adhesion following surgery. However, often during the biodegradation process, these barriers trigger inflammation and cause a foreign body reaction with subsequent decrease in anti-adhesion efficacy. Here, a facile strategy comprising the incorporation of ibuprofen (IBU) into implantable membranes and its sustained release was proposed in order to improve anti-adhesion effects and neurological outcomes, namely to prevent failed back surgery syndrome (FBSS). The combination of free IBU and a newly synthetized polymeric prodrug of IBU, namely poly(hydroxyethyl methacrylate) with ester-linked IBU, was successfully used in order to reduce initial burst drug release and provide sustained drug release from fibrous membranes throughout several weeks. Such release profile was shown useful in preventing both acute and chronic inflammation in rats following laminectomy and membrane implantation. Moreover, histological analysis provided evidence of an excellent anti-adhesion effect, while associated neurological deficits were effectively reduced. Furthermore, the assessment of macrophage density, neovascularization, and related gene expression at the lesion site revealed that a sustained anti-inflammatory effect was achieved with the IBU-loaded proposed fibrous membranes. Results suggested that the COX2 pathway plays an important role in the development epidural fibrosis and arachnoiditis. Overall, this study provided evidence that precisely engineered IBU-loaded electrospun fibrous membranes may be useful in preventing FBSS and able to potentially impact the outcome of patients undergoing spine surgery. [Display omitted]