Calcium-alginate microspheres for sustained curcumin delivery attenuate neuroinflammation and enhance nerve regeneration via suppressing NF-κB/MAPK pathways

Peripheral nerve regeneration is hindered by persistent neuroinflammation. Curcumin, a promising anti-inflammatory agent, is limited by poor bioavailability. To enable localized and sustained delivery, we developed curcumin-loaded calcium-alginate microspheres (Cur@SA-MS), with an encapsulation efficiency of 75.93%, a loading capacity of 7.78%, and a stable two-week release profile, with cumulative release reaching approximately 80% by day 14. In vitro, Cur@SA-MS protected Schwann cells from LPS-induced inflammation by improving cell viability from ∼28% to ∼79% and reducing oxidative injury and inflammatory cytokine levels (TNF-α and IL-6). In a mouse sciatic nerve crush model, a single perineural injection of Cur@SA-MS showed prolonged local retention and significantly improved functional recovery, increasing ipsilateral PWMT from 0.92 g in the model group to 5.00 g and PWL from 3.62 s to 6.12 s at day 14, while preserving myelin integrity and reducing inflammatory infiltration. Integrated transcriptomic and network pharmacology analyses suggested the involvement of NF-κB/MAPK pathways and linked them to broader inflammatory networks. Thus, this study presents Cur@SA-MS as a localized and sustained delivery system that attenuates neuroinflammation and promotes peripheral nerve repair, highlighting its potential as a biomaterials-based strategy for targeted therapy.