Sustained Intra-Articular Lacosamide Delivery Suppresses Catabolism and Alleviates Osteoarthritis Symptoms

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Summary of  Bioactive Materials  https://doi.org/10.1016/j.bioactmat.2026.02.045
Dr. Chaopeng He et al.

Points

Researchers identified the sodium channel Nav1.7 as an overactive target in osteoarthritis chondrocytes that simultaneously accelerates joint tissue degeneration and amplifies pain signaling.
Lacosamide outperformed traditional sodium channel inhibitors by suppressing inflammation-induced tissue breakdown and stimulating cartilage-building proteins at highly optimized, low concentrations.
The molecular mechanism of lacosamide involves triggering the secretion of heat shock protein 70 and midkine to control inflammation and repair tissue.
To prevent rapid joint drainage, a thermoresponsive Collagen II hydrogel was engineered to stay liquid in the syringe and solidify upon injection for sustained drug release.
Monthly localized injections of the lacosamide-loaded hydrogel provided superior structural protection and pain relief in preclinical models compared to standard daily oral medication.

Summary

This study evaluated the therapeutic potential of lacosamide (LCM), an approved epilepsy medication, as a dual-acting, disease-modifying therapy for osteoarthritis (OA). Utilizing primary human OA chondrocytes, cartilage explants, and a murine destabilization of the medial meniscus (DMM) model, researchers investigated LCM’s ability to inhibit the sodium channel Nav1.7. This specific protein becomes overactive in OA, simultaneously driving pain signaling and triggering chondrocytes to degrade cartilage tissue.

In comparative laboratory testing against older sodium channel inhibitors, carbamazepine and oxcarbazepine, LCM demonstrated superior potency in suppressing interleukin-1 beta (IL-1β)–induced catabolism and promoting anabolism. The treatment efficacy followed a finely tuned, non-linear dosing profile, achieving optimal structural and anti-inflammatory benefits at specific low concentrations. Mechanistically, LCM-mediated Nav1.7 inhibition stimulated the cellular secretion of two key protective signaling proteins, heat shock protein 70 (HSP70) and midkine, which mitigate tissue stress and reduce joint inflammation.

To overcome rapid joint clearance, researchers developed a thermoresponsive Collagen II–based hydrogel for sustained intra-articular delivery. Preclinical testing demonstrated that a single intra-articular injection of the LCM-loaded gel administered every four weeks provided enhanced cartilage protection and analgesia compared to daily oral administration, while utilizing only one-tenth of the systemic dose. Given LCM’s established clinical efficacy in treating human Nav1.7-mutation neuropathies, this localized biomaterial delivery system offers a highly translatable, non-opioid strategy for structural preservation and symptom management in OA.

Link to the article: https://www.sciencedirect.com/science/article/pii/S2452199X26001064?via%3Dihub

References

He, C., Huang, G., Moradi, L., Bi, J., Yang, X., Liu, X., Cui, X., Varthi, A., Wiznia, D. H., Waxman, S. G., Fu, W., & Liu, C.-J. (2026). Collagen II hydrogel-mediated sustained delivery of lacosamide attenuates cartilage degeneration and pain in osteoarthritis. Bioactive Materials, 61, 640–656. https://doi.org/10.1016/j.bioactmat.2026.02.045