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

  • ACS Appl Mater Interfaces. 2026 Jun 3;18(21):29739-29755. doi: 10.1021/acsami.6c05534.
Jidi Liu  1 ,  Huicong Feng  1  2 ,  Yingqi Liu  1 ,  Tong Zhu  3 ,  Han Wang  4 ,  Jing Wang  4 ,  Fu Zhu  4 ,  Shuang Gao  1 ,  Xinru Wang  1 ,  Rusi Zhang  5 ,  Xifan Mei  2  6  7 ,  Chao Wu  2  4 ,  He Tian  1  2
Affiliations
  • 1. School of Basic Medicine, Jinzhou Medical University, Jinzhou, Liaoning 121001, China.
  • 2. Liaoning Provincial Collaborative Innovation Center of Medical Testing and Drug Development, Jinzhou Medical University, Jinzhou, Liaoning 121001, China.
  • 3. First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China.
  • 4. School of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning 121001, China.
  • 5. Dalian Medical University, Dalian, Liaoning 116044, China.
  • 6. Liaoning Provincial Key Laboratory of Medical Tissue Engineering, Jinzhou Medical University, Jinzhou, Liaoning 121001, China.
  • 7. Liaoning Vocational College of Medicine, Shenyang, Liaoning 110101, China.
PMID: 42176032 DOI: 10.1021/acsami.6c05534
Abstract

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.

Keywords
chitosan; inflammation; liposomes; methyl eugenol; spinal cord injury.
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