Efficacy and Application Scenarios of Chondroitin Sulfate

Chondroitin sulfate (CAS: 9007-28-7) is a natural amino polysaccharide predominantly found in human connective tissue, skin, and eyes. This polysaccharide consists of repeated disaccharide units, primarily made up of glucuronic acid and N-acetylgalactosamine, linked to the serine residue of a core protein via a sugar linkage region.

 

Chondroitin sulfate can be extracted from the cartilage of various animals, including sharks, cattle, pigs, and chickens. It has a broad spectrum of applications in the biomedical field. Commonly, chondroitin sulfate is used to treat arthritis and enhance bone quality. Additionally, it is utilized to improve corneal hydration, promote wound healing, and treat a variety of conditions such as neuralgic headaches and cardiovascular and cerebrovascular diseases.

 

 

 

Chondroitin Sulfate Products

 

CAS: 9007-28-7

Molecular formula: C13H21NO15S

Molecular weight: 463.36854

Storage conditions: cool place

 

 

 

Chondroitin Sulfate Benefits

 

Treatment of Osteoarthritis and Other Joint Diseases:

Chondroitin sulfate is effective in treating various joint diseases, including osteoarthritis, rheumatoid arthritis, frozen shoulder, and synovitis. It promotes the metabolism of chondrocytes and improves blood circulation in articular cartilage, thereby alleviating joint inflammation. Additionally, it enhances the synthesis and quality of articular cartilage.

 

Promote Wound Healing:

Chondroitin sulfate accelerates wound repair by promoting granulation formation. Its utilization of animal mucopolysaccharides helps prevent post-surgical adhesions, facilitating quicker and more efficient healing processes.

 

Improve Joint Problems:

For conditions such as senile degenerative arthritis and rheumatoid arthritis, chondroitin sulfate plays a crucial role in maintaining joint health. It helps retain water in the body and supports the digestion, absorption, transportation, and metabolism of nutrients, thereby improving joint function and alleviating problems.

 

Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases:

Chondroitin sulfate promotes angiogenesis and enhances microcirculation, providing supportive treatment for cardiovascular and cerebrovascular diseases. It helps manage hyperlipidemia and significantly reduces plasma cholesterol levels, preventing the formation of atherosclerosis.

 

Relieve Neuropathic and Muscle Pain:

Chondroitin sulfate is beneficial for alleviating various types of pain, including neuralgia, neuropathic migraines, joint pain, arthritis, and scapular joint pain. It can also be used to relieve post-surgical pain and hearing loss caused by streptomycin, as well as hearing difficulties and tinnitus due to noise exposure.

 

Ophthalmic Applications:

In ophthalmology, chondroitin sulfate is used to promote corneal hydration and improve microcirculation. It protects the cornea and aids in the repair of corneal tissue damage, thereby enhancing overall eye health.

 

 

Food Application

 

Risk Assessment of Chondroitin Sulfate in Food Supplements

The safety and risks associated with chondroitin sulfate in food supplements have been evaluated extensively. While chondroitin sulfate is a natural component of articular cartilage and widely used in food supplements, it is not approved as an oral medication for joint diseases in Germany. For food supplements, safety is paramount, and they must not pose any health risks. Additionally, the ingredients should not have significant pharmacological effects. Ensuring the safety and regulatory oversight of food supplements is critical to protecting consumer health.

 

The Role of Sea Cucumber Chondroitin Sulfate Polysaccharide in Alleviating Food Allergies

Research has demonstrated that sea cucumber chondroitin sulfate (SCCS) has significant anti-allergic properties compared to shark, bovine, and porcine chondroitin sulfates. SCCS effectively inhibits the degranulation of RBL-2H3 cells, reduces allergic symptoms in mice, and promotes the secretion of mucin 2 (MUC2) and differentiation of regulatory T cells. It achieves these effects by increasing the proportion of specific intestinal flora and short-chain fatty acids. This study enhances our understanding of SCCS's mechanism in alleviating food allergies.

 

Preparation Technology of Canned Ray Surimi Rich in Chondroitin Sulfate

Development of canned fish products rich in chondroitin sulfate, such as "ray and cod in white sauce" and "ray and cod meatballs in tomato sauce," has been achieved. Each can contains 550 to 700 mg of chondroitin sulfate, ensuring 78% to 100% of the daily intake. The production process includes infrared blanching to remove urea from fish meat and optimization of the formula and sterilization mode. This study provides technical support for creating functional foods rich in chondroitin sulfate, ensuring product safety and quality.

 

Zein-Based Self-Assembled Composite Nanoparticles as a Delivery Vehicle for Curcumin

Composite nanoparticles made from zein and chondroitin sulfate (CS) have been prepared to load curcumin (ZCCNPs) using the anti-solvent precipitation method. The increase in CS alters the structure of ZCCNPs from spherical to microaggregates, involving hydrogen bonding, electrostatic, and hydrophobic interactions. CS enhances the anti-denaturation capacity and encapsulation efficiency of curcumin, with an optimal encapsulation efficiency of 91.97%. In vitro studies show that ZCCNPs improve the antiproliferative activity and bioaccessibility of curcumin on HCT116 cells and exhibit good biocompatibility with NCM460 cells. These findings suggest that CS enhances the performance of curcumin-loaded nanoparticles, making them promising for functional food applications.

 

Determination of Chondroitin Sulfate in Health Food by HPLC

A rapid and straightforward HPLC method for determining chondroitin sulfate in health foods has been established. The method demonstrates a good linear relationship within the range of 0.008-0.04 mg/mL, with an average recovery rate of 98.5%-100.0% and an RSD of 0.6%. This method offers rapidity, simplicity, accuracy, and good reproducibility, making it suitable for laboratory promotion and application in determining chondroitin sulfate in health foods.

 

 

Medical Applications

 

The Role of Chondroitin Sulfate E in Angiogenesis

Chondroitin sulfate E (CS-E) is a specific glycosaminoglycan characterized by E-type disaccharide units sulfated at both the C-4 and C-6 positions of N-acetylgalactosamine. CS-E forms chondroitin sulfate proteoglycans (PGs) by covalently linking to core proteins, which can be either secreted or associated with the plasma membrane. These PGs selectively interact with growth factors and chemokines, playing crucial roles in regulating various cellular and tissue processes, including angiogenesis.

 

Effects of Chondroitin Sulfate After Spinal Cord Injury

Spinal cord injury results in both acute and chronic changes, ultimately leading to the formation of a glial scar. This scar comprises fibroblasts, macrophages, microglia, and reactive astrocytes, and accumulates extracellular matrix (ECM) molecules, predominantly chondroitin sulfate proteoglycans (CSPGs). CSPGs in the glial scar are known to inhibit axon regeneration by interacting with receptors and inhibiting plasticity and regeneration through their sulfated glycosaminoglycan (GAG) chains. Understanding the inhibitory role of CSPGs in glial scars is critical for developing new therapies aimed at enhancing neural repair and regeneration.

 

Chondroitin Sulfate Proteoglycans as an Emerging Therapeutic Strategy for Central Nervous System Injuries

CSPGs are major components of glial scars formed after central nervous system (CNS) injuries, and they significantly inhibit axon regeneration. Therapeutic strategies that focus on degrading the glycosaminoglycan skeleton of CSPGs aim to reduce their inhibitory effects, thereby promoting repair after CNS injury. By selectively degrading CSPGs, these strategies enhance the extension of neurite growth cones and improve axonal regeneration. This approach holds promise for developing new treatments for CNS injuries, offering new hope for patients suffering from these conditions.

 

 

Drug Delivery

 

Chondroitin sulfate functionalized nanoparticles for colon macrophage-targeted drug delivery

Chondroitin sulfate (CS) was conjugated to the surface of polymeric nanoparticles (NPs) for colonic macrophage-targeted drug delivery. The average diameter of CS-bound NPs (CS-NPs) is 281 nm, the size distribution is monodisperse, and the surface is negatively charged. CS-NPs showed excellent biocompatibility and high cellular internalization efficiency in Raw 264.7 macrophages. CS-NPs showed a significantly stronger ability than carboxymethylcellulose-functionalized CUR-encapsulated NPs (CUL-NPs) in inhibiting the secretion of major pro-inflammatory cytokines by lipopolysaccharide-stimulated macrophages. Orally administered chitosan/alginate hydrogel-embedded CS-NPs are more effective than CUL-NPs in the treatment of ulcerative colitis (UC). CS-NP-embedded hydrogel is expected to be developed as a macrophage-targeted drug delivery system for the treatment of UC.

 

Chondroitin Sulfate Functionalized Polymer Nanoparticles for Targeted Chemotherapy of Colon Cancer

To enhance the targeted delivery of chemotherapy drugs for colon cancer, camptothecin (CPT) has been loaded into polymeric nanoparticles (NPs) and functionalized with chondroitin sulfate (CS). The resulting CS-CPT-NPs have an optimal hydrodynamic diameter of 289 nm, a narrow particle size distribution (polydispersity index = 0.192), and a neutral surface charge. In vitro studies reveal that CS surface functionalization significantly enhances the NPs' ability to target colon cancer cells, improving their anti-cancer activity and pro-apoptotic effects. In vivo experiments with mice bearing colon tumors demonstrate that CS-CPT-NPs achieve better therapeutic outcomes compared to non-targeting NPs, without inducing systemic toxicity. This indicates that CS-CPT-NPs are a promising drug delivery system for the targeted chemotherapy of colon cancer.

 

Chondroitin sulfate (CS) was conjugated to zein (zein) to form hybrid nanoparticles (zein/CS NPs), which were developed for targeted delivery of docetaxel. Zein/CS NPs showed better colloidal stability and maintained their initial size for 12 h in serum. Pretreatment with CS reduced the uptake efficiency of NPs in PC-3 cells by 23%, indicating that CS was involved in the CD44-mediated uptake mechanism. The IC50 value of zein/CS NPs was 2.79-fold lower than that of free docetaxel. The tumor accumulation of NPs in PC-3 xenograft mice was enhanced by 35.3-fold (compared with free Cy5.5). NPs showed better pharmacokinetic properties, with a 9.5-fold longer terminal half-life, comparable antitumor efficacy to Taxotere, and negligible systemic toxicity.

 

Hybrid nanoparticles composed of chondroitin sulfate (CS) and zein have been developed for the targeted delivery of docetaxel, a chemotherapeutic agent. These zein/CS nanoparticles (zein/CS NPs) exhibit improved colloidal stability and maintain their initial size for 12 hours in serum. Pretreatment with CS reduces the uptake efficiency of NPs in PC-3 cells by 23%, suggesting the involvement of a CD44-mediated uptake mechanism. The IC50 value of zein/CS NPs is 2.79 times lower than that of free docetaxel, indicating higher efficacy. Near-infrared fluorescence imaging shows that the accumulation of NPs in tumors of PC-3 xenograft mice is increased by 35.3 times compared to free Cy5.5. Additionally, these NPs demonstrate better pharmacokinetic properties, including a 9.5-fold longer terminal half-life, comparable antitumor efficacy to Taxotere, and negligible systemic toxicity. This suggests that zein/CS NPs are an effective vehicle for tumor-targeted delivery of docetaxel.

 

 

Novel Medical Material

 

Chitosan-Chondroitin Sulfate-Based Polyelectrolyte Complexes for Treating Chronic Wounds

Polyelectrolyte complexes (PECs) made from chitosan (CH) and chondroitin sulfate (CS) have shown significant promise in treating chronic wounds. The preparation of these PECs was optimized using a quality by design (QbD) approach. The resulting PECs exhibited high swellability and porosity, were non-hemolytic, had good blood compatibility with a low coagulation index, and demonstrated strong antimicrobial activity against both Gram-positive and Gram-negative bacteria. Cell proliferation studies indicated that CH-CS PECs are biocompatible and can significantly enhance cell density, showing a nearly fourfold increase compared to the control group. These results suggest that CH-CS PECs are ideal for wound dressing materials due to their good blood compatibility, high antimicrobial effectiveness, and ability to promote wound healing by stimulating fibroblast growth.

 

Chondroitin Sulfate Glycosaminoglycan Scaffolds for Bone Regeneration

Chondroitin sulfate glycosaminoglycan (CS-GAG) scaffolds have been studied as a delivery vehicle for recombinant human bone morphogenetic protein 2 (rhBMP-2), in comparison to the clinical standard collagen sponge. The CS-GAG scaffold was found to prolong the release of rhBMP-2 more effectively than the collagen sponge. Additionally, mesenchymal stem cells (BMP-2 MSCs) expressing rhBMP-2 also showed a prolonged release when inserted into the CS-GAG scaffold. In a challenging critical-sized femoral defect model in rats, both rhBMP-2 and BMP-2 MSCs delivered via the CS-GAG scaffold induced bone formation comparable to rhBMP-2 delivered by the collagen sponge, as indicated by measurements of bone volume, strength, and stiffness. These findings suggest that CS-GAG scaffolds are a promising delivery vehicle for the controlled release of rhBMP-2, effectively promoting the repair of critical-sized segmental bone defects.

 

Collagen and Chondroitin Sulfate Functionalized Biomimetic Fibers for Tendon Tissue Engineering

Highly aligned poly(L-lactic acid) (PLLA) fibers functionalized with type 1 collagen (COL1) and chondroitin sulfate (CS) have been fabricated using a coaxial stabilized jet electrospinning method. Compared to ordinary PLLA fibers, these biomimetic COL1-CS/PLLA fibers significantly improved cell spreading and proliferation rates. The expression of tendon-related genes such as scleraxis (SCX) and COL1, as well as the protein tenomodulin (TNMD), was notably increased. Additionally, mechanical stimulation had a synergistic effect on the tenogenic differentiation of human mesenchymal stem cells (hMSCs), activating the TGF-β signaling pathway and promoting tenogenic differentiation. In animal experiments, the COL1-CS/PLLA scaffold effectively promoted tendon-like tissue regeneration in rat Achilles tendon repairs. Therefore, these biomimetic fibers represent a potent scaffold system for functional tendon regeneration.

 

 

References:

 

1. Li, C., Tian, Y., Pei, J., Zhang, Y., Hao, D., Han, T., Wang, X., Song, S., Huang, L., & Wang, Z. (2023). Sea cucumber chondroitin sulfate polysaccharides attenuate OVA-induced food allergy in BALB/c mice associated with gut microbiota metabolism and Treg cell differentiation. Food & Function. https://doi.org/10.1039/d3fo00146f

2. Stellavato, A., Restaino, O. F., Vassallo, V., Finamore, R., Ruosi, C., Cassese, E., de Rosa, M., & Schiraldi, C. (2019). Comparative analyses of pharmaceuticals or food supplements containing chondroitin sulfate: Are their bioactivities equivalent? Advances in Therapy, 36(12), 3221-3237. https://doi.org/10.1007/s12325-019-01064-8

3. Raybulov, S., & Shokina, Y. (2020). Technology of minced fish canned food from thorny skate, enriched with chondroitin sulfate. KnE Life Sciences, 5(1), 819–835.

4. Caiyun, C., Weijiang, C., Hongbi, C., & XianBang, L. (2015). Determination of chondroitin sulfate in health food by high performance liquid chromatography. Journal of Food Safety and Quality, 6, 1913-1918. https://api.semanticscholar.org/CorpusID:101988539

5. Kastana, P., Choleva, E., Poimenidi, E., Karamanos, N., Sugahara, K., & Papadimitriou, E. (2019). Insight into the role of chondroitin sulfate E in angiogenesis. The FEBS Journal, 286(15), 1-15. https://doi.org/10.1111/febs.14830

6. Hussein, R. K., Mencio, C., Katagiri, Y., Brake, A. M., & Geller, H. M. (2020). Role of chondroitin sulfation following spinal cord injury. Frontiers in Cellular Neuroscience, 14. https://doi.org/10.3389/fncel.2020.00208

7. Mukherjee, N., Nandi, S., Garg, S., Ghosh, S., Ghosh, S., Samat, R., & Ghosh, S. (2020). Targeting chondroitin sulfate proteoglycans: An emerging therapeutic strategy to treat CNS injury. ACS Chemical Neuroscience. https://doi.org/10.1021/acschemneuro.0c00004

8. Stephenson, E., Mishra, M. K., Moussienko, D., Laflamme, N., Rivest, S., Ling, C.-C., & Yong, V. W. (2018). Chondroitin sulfate proteoglycans as novel drivers of leucocyte infiltration in multiple sclerosis. Brain, 141, 1094–1110.

9. Zhang, X., Ma, Y., Ma, L., Zu, M., Song, H., & Xiao, B. (2019). Oral administration of chondroitin sulfate-functionalized nanoparticles for colonic macrophage-targeted drug delivery. Carbohydrate Polymers, 223, 115126. https://doi.org/10.1016/j.carbpol.2019.115126

10. Zu, M., Ma, L., Zhang, X., Xie, D., Kang, Y., & Xiao, B. (2019). Chondroitin sulfate-functionalized polymeric nanoparticles for colon cancer-targeted chemotherapy. Colloids and Surfaces B: Biointerfaces, 177, 399-406.

11. Lee, H. S., Kang, N., Kim, H., Kim, D. H., Chae, J., Lee, W., ... Kim, D. D., & Lee, J. Y. (2021). Chondroitin sulfate-hybridized zein nanoparticles for tumor-targeted delivery of docetaxel. Carbohydrate Polymers, 253, 117187.

12. Sharma, S., Swetha, K., & Roy, A. (2019). Chitosan-chondroitin sulfate based polyelectrolyte complex for effective management of chronic wounds. International Journal of Biological Macromolecules, 132, 97-108. https://doi.org/10.1016/j.ijbiomac.2019.03.186

13. Andrews, S. H., Cheng, A., Stevens, H. Y., Logun, M. T., Webb, R. L., Jordan, E. T., Xia, B., Karumbaiah, L., Guldberg, R. E., & Stice, S. L. (2019). Chondroitin sulfate glycosaminoglycan scaffolds for cell and recombinant protein‐based bone regeneration. Stem Cells Translational Medicine, 8(4), 575-585.

14. Yuan, H., Li, X., Lee, M.-S., Zhang, Z., Li, B., Xuan, H., Li, W.-J., & Zhang, Y. (2020). Collagen and chondroitin sulfate functionalized bioinspired fibers for tendon tissue engineering application. International Journal of Biological Macromolecules. https://doi.org/10.1016/j.ijbiomac.2020.12.152