Glutathione-Chitosan Modified Methyl Eugenol Liposomes Promote Spinal Cord Injury Repair by Alleviating Neuroinflammation

Spinal cord injury (SCI) is a highly disabling trauma, and the inflammatory response plays a critical role in disease progression. The detrimental inflammatory microenvironment exacerbates neuronal apoptosis and suppresses axonal regeneration. Methyl eugenol (ME), the primary active ingredient in the traditional Chinese medicine Asarum, possesses multiple pharmacological activities, including anti-inflammatory and antioxidant. In this study, we developed glutathione-chitosan modified ME liposomes (GCME-LIPO) for the intranasal delivery in SCI treatment. The GCME-LIPO was achieved by encapsulating ME in liposomes, chitosan was electrostatically adsorbed on the surface to enhance mucosal adhesion, and Glutathione was covalently bonded to the amino groups of chitosan. The nanoparticles were well-dispersed, approximately 200 nm in size, and biocompatible. Following intranasal administration, GCME-LIPO showed enhanced accumulation in the injured spinal cord and increased localization around microglia. Both in vitro and in vivo experiments confirmed that GCME-LIPO significantly downregulated the expressions of TNF-α, iNOS and IL-1β and upregulated the levels of IL-4 and Arg-1. In addition, motor function in SCI mice was significantly improved after GCME-LIPO treatment. The underlying mechanism of GCME-LIPO was associated with the inhibition of the JAK2/STAT3 signaling pathway activation. This study provides a strategy for applying ME in SCI treatment, demonstrating considerable application potential.