The effects of withaferin A-conjugated mesoporous silica nanoparticles on sciatic nerve regeneration in male wistar rats.

AIMS: This research evaluated the efficacy of Withaferin A-conjugated mesoporous silica nanoparticles (WA-MSNs) in accelerating the restoration of neural tissue and improving the recovery of sensory and motor functions following a sciatic nerve injury (SNI) in male Wistar rats.

METHODS

WA-MSNs were evaluated for encapsulation efficiency, drug release, particle size, surface charge, and molecular interactions. A rat SNI model was created, and subjects were treated with WA-MSNs, free WA, unloaded MSNs, or received no treatment. The sham group was also included for comparison. Regeneration was measured through the sciatic functional index (SFI), Hargreaves test, and electrophysiology (CMAP and NCV). Complementary assessments included sciatic nerve histomorphometry, assessment of gastrocnemius muscle mass, and Enzyme-Linked Immunosorbent Assay (ELISA) for inflammatory cytokines and neurotrophic factors.

RESULTS

WA-MSNs achieved a 74.6% encapsulation efficiency and provided sustained drug release over 72 h. DLS analysis showed a monodisperse colloidal system, with an average hydrodynamic diameter of approximately 198 nm and a zeta potential of -22.4 mV. WA-MSN-treated rats exhibited significantly faster motor and sensory recovery compared to controls (p < 0.001), with electrophysiological parameters approaching those of sham-treated rats. Histological analysis revealed improved axonal morphology, myelination, and recovery of gastrocnemius muscle mass. ELISA results showed modulation of cytokine profiles, characterized by a marked reduction in (IL-1β, IL-6, TNF-α), and substantial elevation in the levels of (IL-10, TGF-β), and elevated neurotrophic factors (NGF, BDNF, NT-3).

CONCLUSION

WA-MSNs significantly promote functional and histological nerve regeneration after SNI by modulating inflammation and enhancing neurotrophic support. These findings support WA-MSNs as a promising therapeutic approach for clinical peripheral nerve repair.