Intradiscal Delivery of Notoginsenoside R1‐Loaded PLGA Nanoparticles Attenuates Intervertebral Disc Degeneration in Rats

Abstract

Intervertebral disc degeneration (IVDD) contributes to persistent low back pain, but existing treatments focus on symptom relief rather than addressing the degeneration. Notoginsenoside R1 (NR1), a bioactive saponin derived from Panax notoginseng, has exhibited protective effects in experimental models of disc injury. However, its clinical application is limited by poor bioavailability and rapid clearance. Here, NR1 was encapsulated into poly(lactic‐co‐glycolic acid) nanoparticles (NR1@PLGA) to improve local drug retention. NR1@PLGA showed uniform particle characteristics, prolonged NR1 release, and time‐dependent uptake by nucleus pulposus cells (NPCs). Under H2O2‐induced oxidative stress, NR1@PLGA reduced SA‐β‐gal‐positive cells, preserved aggrecan and collagen II (Col‐2) expression, and improved cell viability compared with free NR1 at the same concentration. In a rat caudal puncture model, intradiscal administration of NR1@PLGA preserved T2‐weighted MRI signals, improved histological outcomes, increased aggrecan expression, and decreased MMP‐13 levels. No obvious abnormalities were observed in major organs or serum biochemical indicators related to liver and kidney function during the 4‐week observation period. These results demonstrate that NR1@PLGA is a potential treatment for IVDD, with PLGA encapsulation enhancing the efficacy of NR1.