Paravertebrally-Injected Multifunctional Hydrogel for Sustained Anti-Inflammation and Pain Relief in Lumbar Disc Herniation.

Abstract

Pain caused by lumbar disc herniation (LDH) severely compromises patients' quality of life. The combination of steroid and local anesthetics is routinely employed in clinics to alleviate LDH-induced pain. However, the approach only mediates transient efficacy and requires repeated and invasive lumbar epidural injections. Here a paravertebrally-injected multifunctional hydrogel that can efficiently co-load and controlled release glucocorticoid betamethasone and anesthetics ropivacaine for sustained anti-inflammation, reactive oxygen species (ROS)-removal and pain relief in LDH is presented. Betamethasone is conjugated to hyaluronic acid (HA) via ROS-responsive crosslinker to form amphiphilic polymer that self-assemble into particles with ropivacaine loaded into the core. Solution of drug-loaded particles and thermo-sensitive polymer rapidly forms therapeutic hydrogel in situ upon injection next to the herniated disc, thus avoiding invasive epidural injection. In a rat model of LDH, multifunctional hydrogel maintains the local drug concentration 72 times longer than free drugs and more effectively inhibits the expression of pro-inflammatory cytokines and pain-related molecules including cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE₂). Therapeutic hydrogel suppresses the LDH-induced pain in rats for 12 days while the equivalent dose of free drugs is only effective for 3 days. This platform is also applicable to ameliorate pain caused by other spine-related diseases.