A study of locally injecting curcumin-loaded mesoporous silica nanoparticles in delaying coccygeal intervertebral disc degeneration in rats_West China Medical Journal

Authors：

LI Jianhua ¹ , WU Ruibang ¹ , LIU Zheng ² , HUANG Yong ¹ ,  FENG Ganjun ¹ , ZHANG Li ² , LIU Limin ¹ , SONG Yueming ¹

1. Department of Orthopedics and Institute of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Analytical & Testing Center, Sichuan University, Chengdu, Sichuan 610064, P. R. China;

Corresponding author：

FENG Ganjun, Email: gjfenghx@wchscu.cn

Keywords：

Intervertebral disc degeneration; curcumin; mesoporous silica; nanoparticles

DOI：

10.7507/1002-0179.202312144

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect of local injection of curcumin-loaded mesoporous silica nanoparticles (Cur@MSN) on the repair and treatment of degenerative intervertebral disc tissue in rats, and provide a new strategy for the treatment of intervertebral disc degeneration. Methods Mesoporous silica nanoparticles (MSN) and Cur@MSN were prepared according to the method reported in the literature. Rat nucleus pulposus cells were co-cultured with curcumin and Cur@MSN, respectively, and the growth status and activity of cells in normal environment and inflammatory environment (adding lipopolysaccharide) were observed respectively. Twelve 8-week-old SD rats were randomly divided into 4 groups, including normal group, degeneration group, curcumin group, and Cur@MSN group, with 3 rats in each group. Acupuncture degeneration model was established in coccygeal intervertebral discs (Co_7-8, Co_8-9) of rats, and corresponding intervention were injected. Imaging, gross pathology, and histological examination were performed after 4 weeks, respectively, to observe the tissue structure and pathological changes of intervertebral discs. Results Under scanning electron microscope, Cur@MSN was spherical in shape, with groove-like pores on its surface. Particle size analysis showed that the particle size of MSN was concentrated in 120-160 nm, and that of Cur@MSN was distributed in 130-170 nm. Zeta potential analysis showed that the average Zeta potential of MSN, curcumin, and Cur@MSN was −12.5, −22.5 and −13.5 mV, respectively. The entrapment efficiency of Cur@MSN was 20.4%, and the drug loading rate was 0.2%. Curcumin released by Cur@MSN in 12 h accounted for about 60% of the total drug dose, and curcumin released in 28 h accounted for about 70%. In cell experiment, there was no significant difference in cell proliferation absorbance among the groups in normal environment (P>0.05), but the cell proliferation absorbance in the Cur@MSN group on the 3rd and 5th day in inflammatory environment was significantly higher than that in the control group and the curcumin group (P<0.01). The percentage of disc height index and the Pfirrmann grade of the Cur@MSN group were better than those of the degeneration group and the curcumin group (P<0.01). The histological score of the Cur@MSN group was lower than that of the degeneration group and the curcumin group (P<0.01). Conclusions Cur@MSN can delay the degeneration process of rat coccygeal intervertebral disc, and has certain repair and treatment effects on its degenerated intervertebral disc. Among them, curcumin can delay the degeneration of intervertebral disc by inhibiting inflammation, and the loading of MSN is helpful for curcumin to exert its biological effects.

Citation： LI Jianhua, WU Ruibang, LIU Zheng, HUANG Yong, FENG Ganjun, ZHANG Li, LIU Limin, SONG Yueming. A study of locally injecting curcumin-loaded mesoporous silica nanoparticles in delaying coccygeal intervertebral disc degeneration in rats. West China Medical Journal, 2024, 39(4): 604-612. doi: 10.7507/1002-0179.202312144 Copy

1.	Hartvigsen J, Hancock MJ, Kongsted A, et al. What low back pain is and why we need to pay attention. Lancet, 2018, 391(10137): 2356-2367.
2.	Lyu FJ, Cui H, Pan H, et al. Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions. Bone Res, 2021, 9(1): 7.
3.	Song C, Zhou Y, Cheng K, et al. Cellular senescence - molecular mechanisms of intervertebral disc degeneration from an immune perspective. Biomed Pharmacother, 2023, 162: 114711.
4.	Jha R, Bernstock JD, Chalif JI, et al. Updates on pathophysiology of discogenic back pain. J Clin Med, 2023, 12(21): 6907.
5.	Shnayder NA, Ashhotov AV, Trefilova VV, et al. Cytokine imbalance as a biomarker of intervertebral disk degeneration. Int J Mol Sci, 2023, 24(3): 2360.
6.	Desmoulin GT, Pradhan V, Milner TE. Mechanical aspects of intervertebral disc injury and implications on biomechanics. Spine (Phila Pa 1976), 2020, 45(8): E457-E464.
7.	Xin J, Wang Y, Zheng Z, et al. Treatment of intervertebral disc degeneration. Orthop Surg, 2022, 14(7): 1271-1280.
8.	Ying Y, Cai K, Cai X, et al. Recent advances in the repair of degenerative intervertebral disc for preclinical applications. Front Bioeng Biotechnol, 2023, 11: 1259731.
9.	Eisenstein SM, Balain B, Roberts S. Current treatment options for intervertebral disc pathologies. Cartilage, 2020, 11(2): 143-151.
10.	Gupta J, Quadros M, Momin M. Mesoporous silica nanoparticles: synthesis and multifaceted functionalization for controlled drug delivery. J Drug Deliv Sci Technol, 2023, 81: 104305.
11.	Pan S, Yan J, Xu X, et al. Current development and future application prospects of plants-derived polyphenol bioactive substance curcumin as a novel feed additive in livestock and poultry. Int J Mol Sci, 2022, 23(19): 11905.
12.	Qiu C, Zhang JZ, Wu B, et al. Advanced application of nanotechnology in active constituents of traditional Chinese medicines. J Nanobiotechnology, 2023, 21(1): 456.
13.	Wang Y, Song H, Yang Y, et al. Kinetically controlled dendritic mesoporous silica nanoparticles: from dahlia- to pomegranate-like structures by micelle filling. Chem Mater, 2018, 30(16): 5770-5776.
14.	芮云峰, 王善正, 谢鑫荟, 等. 大鼠椎间盘髓核来源间充质干细胞的体外分离及培养鉴定. 中国组织工程研究, 2013(49): 8576-8582.
15.	Peng Y, Ao M, Dong B, et al. Anti-inflammatory effects of curcumin in the inflammatory diseases: status, limitations and countermeasures. Drug Des Devel Ther, 2021, 15: 4503-4525.
16.	He Q, Shi J, Chen F, et al. An anticancer drug delivery system based on surfactant-templated mesoporous silica nanoparticles. Biomaterials, 2010, 31(12): 3335-3346.
17.	Cheng Y, Tao J, Zhang Y, et al. Shape and shear stress impact on the toxicity of mesoporous silica nanoparticles: in vitro and in vivo evidence. Mol Pharm, 2023, 20(6): 3187-3201.
18.	Han B, Zhu K, Li FC, et al. A simple disc degeneration model induced by percutaneous needle puncture in the rat tail. Spine (Phila Pa 1976), 2008, 33(18): 1925-1934.
19.	Hu MH, Yang KC, Chen YJ, et al. Optimization of puncture injury to rat caudal disc for mimicking early degeneration of intervertebral disc. J Orthop Res, 2018, 36(1): 202-211.
20.	Oichi T, Taniguchi Y, Soma K, et al. A mouse intervertebral disc degeneration model by surgically induced instability. Spine (Phila Pa 1976), 2018, 43(10): E557-E564.
21.	Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976), 2001, 26(17): 1873-1878.
22.	Ji ML, Jiang H, Zhang XJ, et al. Preclinical development of a microRNA-based therapy for intervertebral disc degeneration. Nat Commun, 2018, 9(1): 5051.
23.	Jose J, Pai AR, Gopakumar DA, et al. Novel 3D porous aerogels engineered at nano scale from cellulose nano fibers and curcumin: an effective treatment for chronic wounds. Carbohydr Polym, 2022, 287: 119338.
24.	Xiang H, Zhao W, Jiang K, et al. Progress in regulating inflammatory biomaterials for intervertebral disc regeneration. Bioact Mater, 2023, 33: 506-531.
25.	Bai J, Zhang Y, Fan Q, et al. Reactive oxygen species-scavenging scaffold with rapamycin for treatment of intervertebral disk degeneration. Adv Healthc Mater, 2020, 9(3): e1901186.
26.	Ma T, Guo CJ, Zhao X, et al. The effect of curcumin on NF-κB expression in rat with lumbar intervertebral disc degeneration. Eur Rev Med Pharmacol Sci, 2015, 19(7): 1305-1314.
27.	Wang Y, Che M, Xin J, et al. The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother, 2020, 131: 110660.
28.	Hu Y, Tang JS, Hou SX, et al. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX-2, TGF-β1/2, MMP-9 and BDNF in a rat model. Mol Med Rep, 2017, 16(5): 6864-6869.

1. Hartvigsen J, Hancock MJ, Kongsted A, et al. What low back pain is and why we need to pay attention. Lancet, 2018, 391(10137): 2356-2367.
2. Lyu FJ, Cui H, Pan H, et al. Painful intervertebral disc degeneration and inflammation: from laboratory evidence to clinical interventions. Bone Res, 2021, 9(1): 7.
3. Song C, Zhou Y, Cheng K, et al. Cellular senescence - molecular mechanisms of intervertebral disc degeneration from an immune perspective. Biomed Pharmacother, 2023, 162: 114711.
4. Jha R, Bernstock JD, Chalif JI, et al. Updates on pathophysiology of discogenic back pain. J Clin Med, 2023, 12(21): 6907.
5. Shnayder NA, Ashhotov AV, Trefilova VV, et al. Cytokine imbalance as a biomarker of intervertebral disk degeneration. Int J Mol Sci, 2023, 24(3): 2360.
6. Desmoulin GT, Pradhan V, Milner TE. Mechanical aspects of intervertebral disc injury and implications on biomechanics. Spine (Phila Pa 1976), 2020, 45(8): E457-E464.
7. Xin J, Wang Y, Zheng Z, et al. Treatment of intervertebral disc degeneration. Orthop Surg, 2022, 14(7): 1271-1280.
8. Ying Y, Cai K, Cai X, et al. Recent advances in the repair of degenerative intervertebral disc for preclinical applications. Front Bioeng Biotechnol, 2023, 11: 1259731.
9. Eisenstein SM, Balain B, Roberts S. Current treatment options for intervertebral disc pathologies. Cartilage, 2020, 11(2): 143-151.
10. Gupta J, Quadros M, Momin M. Mesoporous silica nanoparticles: synthesis and multifaceted functionalization for controlled drug delivery. J Drug Deliv Sci Technol, 2023, 81: 104305.
11. Pan S, Yan J, Xu X, et al. Current development and future application prospects of plants-derived polyphenol bioactive substance curcumin as a novel feed additive in livestock and poultry. Int J Mol Sci, 2022, 23(19): 11905.
12. Qiu C, Zhang JZ, Wu B, et al. Advanced application of nanotechnology in active constituents of traditional Chinese medicines. J Nanobiotechnology, 2023, 21(1): 456.
13. Wang Y, Song H, Yang Y, et al. Kinetically controlled dendritic mesoporous silica nanoparticles: from dahlia- to pomegranate-like structures by micelle filling. Chem Mater, 2018, 30(16): 5770-5776.
14. 芮云峰, 王善正, 谢鑫荟, 等. 大鼠椎间盘髓核来源间充质干细胞的体外分离及培养鉴定. 中国组织工程研究, 2013(49): 8576-8582.
15. Peng Y, Ao M, Dong B, et al. Anti-inflammatory effects of curcumin in the inflammatory diseases: status, limitations and countermeasures. Drug Des Devel Ther, 2021, 15: 4503-4525.
16. He Q, Shi J, Chen F, et al. An anticancer drug delivery system based on surfactant-templated mesoporous silica nanoparticles. Biomaterials, 2010, 31(12): 3335-3346.
17. Cheng Y, Tao J, Zhang Y, et al. Shape and shear stress impact on the toxicity of mesoporous silica nanoparticles: in vitro and in vivo evidence. Mol Pharm, 2023, 20(6): 3187-3201.
18. Han B, Zhu K, Li FC, et al. A simple disc degeneration model induced by percutaneous needle puncture in the rat tail. Spine (Phila Pa 1976), 2008, 33(18): 1925-1934.
19. Hu MH, Yang KC, Chen YJ, et al. Optimization of puncture injury to rat caudal disc for mimicking early degeneration of intervertebral disc. J Orthop Res, 2018, 36(1): 202-211.
20. Oichi T, Taniguchi Y, Soma K, et al. A mouse intervertebral disc degeneration model by surgically induced instability. Spine (Phila Pa 1976), 2018, 43(10): E557-E564.
21. Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976), 2001, 26(17): 1873-1878.
22. Ji ML, Jiang H, Zhang XJ, et al. Preclinical development of a microRNA-based therapy for intervertebral disc degeneration. Nat Commun, 2018, 9(1): 5051.
23. Jose J, Pai AR, Gopakumar DA, et al. Novel 3D porous aerogels engineered at nano scale from cellulose nano fibers and curcumin: an effective treatment for chronic wounds. Carbohydr Polym, 2022, 287: 119338.
24. Xiang H, Zhao W, Jiang K, et al. Progress in regulating inflammatory biomaterials for intervertebral disc regeneration. Bioact Mater, 2023, 33: 506-531.
25. Bai J, Zhang Y, Fan Q, et al. Reactive oxygen species-scavenging scaffold with rapamycin for treatment of intervertebral disk degeneration. Adv Healthc Mater, 2020, 9(3): e1901186.
26. Ma T, Guo CJ, Zhao X, et al. The effect of curcumin on NF-κB expression in rat with lumbar intervertebral disc degeneration. Eur Rev Med Pharmacol Sci, 2015, 19(7): 1305-1314.
27. Wang Y, Che M, Xin J, et al. The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother, 2020, 131: 110660.
28. Hu Y, Tang JS, Hou SX, et al. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX-2, TGF-β1/2, MMP-9 and BDNF in a rat model. Mol Med Rep, 2017, 16(5): 6864-6869.

West China Medical Journal

A study of locally injecting curcumin-loaded mesoporous silica nanoparticles in delaying coccygeal intervertebral disc degeneration in rats

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content