【Animal modeling】-Effect of simvastatin PLGA sustained-release microspheres on intervertebral disc degeneration in rats

  Objective: To investigate the efficacy of local injection of simvastatin PLGA sustained-release microspheres in the treatment of intervertebral disc degeneration in rats.

  Methods: Simvastatin PLGA sustained-release microspheres were prepared by double emulsion method, and the characterization of the microspheres and drug release in vitro were observed. Vastatin PLGA microspheres), the experimental animals were sacrificed 2 and 4 weeks after injection, and evaluated by imaging, histology and molecular biology.

  RESULTS: Simvastatin PLGA sustained-release microspheres were spherical, regular in shape, smooth in surface, average particle size was (1.52±0.54) μm, drug loading rate was (23.3±1.3)%, and encapsulation rate was (90.4±2.6) %. The in vitro drug release test showed that the release rate was 45% in the first 24 hours, and the cumulative release rate in the following 144 hours was over 81.2%. The degree of intervertebral disc degeneration in the experimental group was alleviated after treatment. There were significant differences in gap height index, MRI score, HE staining and toluidine blue staining score (P<0.05). Bone morphogenetic protein-BMP-2, collagen type II, proteoglycan in the experimental group The mRNA expression of hypoxia inducible factor-1α (HIF-1α) was significantly increased compared with the control group (P<0.05).

  Conclusion: The prepared simvastatin PLGA sustained-release microspheres can achieve better sustained-release effect of the drug. Local injection of simvastatin PLGA sustained-release microspheres can improve the degree of intervertebral disc degeneration, and promote type II collagen and proteoglycan in nucleus pulposus tissue. The mechanism may be related to the increased expression of HIF-1α and BMP-2.