Treatment of experimental autoimmune encephalomyelitis by codelivery of disease associated Peptide and dexamethasone in acetalated dextran microparticles.

Abstract

Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system that can cause loss of motor function and is thought to result, in part, from chronic inflammation due to an antigen-specific T cell immune response. Current treatments suppress the immune system without antigen specificity, increasing the risks of cancer, chronic infection, and other long-term side effects. In this study, we show treatment of experimental autoimmune encephalomyelitis (EAE), a model of MS, by coencapsulating the immunodominant peptide of myelin oligodendrocyte glycoprotein (MOG) with dexamethasone (DXM) into acetalated dextran (Ac-DEX) microparticles (DXM/MOG/MPs) and administering the microparticles subcutaneously. The clinical score of the mice was reduced from 3.4 to 1.6 after 3 injections 3 days apart with the coencapsulated microparticulate formulation (MOG 17.6 μg and DXM 8 μg). This change in clinical score was significantly greater than observed with phosphate-buffered saline (PBS), empty MPs, free DXM and MOG, DXM/MPs, and MOG/MPs. Additionally, treatment with DXM/MOG/MPs significantly inhibited disease-associated cytokine (e.g., IL-17, GM-CSF) expression in splenocytes isolated in treated mice. Here we show a promising approach for the therapeutic treatment of MS using a polymer-based microparticle delivery platform.

• Authors: Kevin J Peine, Mireia Guerau-de-Arellano, Priscilla Lee, Naveen Kanthamneni, Mary Severin, G Duane Probst, Haiyan Peng, Yuhong Yang, Zachary Vangundy, Tracey L Papenfuss, Amy E Lovett-Racke, Eric M Bachelder, Kristy M Ainslie
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 11 Issue 3 Pg. 828-35 (Mar 03 2014) ISSN: 1543-8392 [Electronic] United States
• PMID: 24433027 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Cytokines
• Dextrans
• Mog protein, mouse
• Myelin-Oligodendrocyte Glycoprotein
• Peptide Fragments
• Polymers
• Nitric Oxide
• Dexamethasone

Topics

• Animals
• Cell Proliferation (drug effects)
• Combined Modality Therapy
• Cytokines (metabolism)
• Dexamethasone (administration & dosage, pharmacokinetics)
• Dextrans (chemistry)
• Drug Delivery Systems
• Encephalomyelitis, Autoimmune, Experimental (immunology, pathology, therapy)
• Female
• Flow Cytometry
• Mice
• Mice, Inbred C57BL
• Myelin-Oligodendrocyte Glycoprotein (immunology, metabolism)
• Nitric Oxide (metabolism)
• Peptide Fragments (administration & dosage, immunology)
• Polymers (chemistry)
• Tissue Distribution