Intervertebral disc degeneration (IVDD) and related inflammatory pain conditions require innovative therapeutic approaches for effective management. In this study, a lipidic prodrug of diclofenac, Diclofenac Lauryl Ester (L-DCF), was synthesized and formulated into nanoparticles (Nanofenac-L) using the ethanol injection method followed by microfluidization. The physicochemical characterization of Nanofenac-L confirmed high encapsulation efficiency (%EE > 97%) and sustained drug release, reaching approximately 65% diclofenac acid release within 48 hours. In vitro efficacy studies demonstrated a significant downregulation of pain marker Substance P by Nanofenac-L, whereas COX-2 expression was more effectively reduced by diclofenac sodium (DCF-Na). Antioxidant markers (GPX1, PRDX1, and SOD1) were upregulated in nucleus pulposus cells (NPCs), with Nanofenac-L showing a more pronounced effect on PRDX1. Although preventive treatment showed limited efficacy, the curative treatment regimen demonstrated significant therapeutic potential. These findings suggest that Nanofenac-L is a promising anti-inflammatory, analgesic, and antioxidant candidate for IVDD and other pain-related conditions. Further preclinical and clinical studies are warranted to validate its translational potential