Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, United States.
Bioengineering Graduate Program, University of Kansas, Lawrence, KS, United States.
J Control Release. 2017 Nov 28;266:156-165. doi: 10.1016/j.jconrel.2017.09.034. Epub 2017 Sep 28.
Current therapies for autoimmune diseases focus on treating the symptoms rather than the underlying disease cause. A major setback in improving current therapeutics for autoimmunity is the lack of antigen specificity. Successful antigen-specific immunotherapy (ASIT) would allow for improved treatment of autoimmune diseases. In this work, dexamethasone was co-delivered with autoantigen (PLP) in vivo to create effective ASIT for the treatment of experimental autoimmune encephalomyelitis (EAE). Using an emulsion of incomplete Freund's adjuvant (IFA) as a co-delivery vehicle, it was discovered that the controlled release of autoantigen was important for the suppression of clinical disease symptoms. Analysis of the immune response via cytokines revealed that dexamethasone was important for shifting the immune response away from inflammation. Co-delivery of both autoantigen and dexamethasone increased B-cell populations and antibody production, signifying an increased humoral immune response. Overall, this data indicated that the co-delivery of PLP and dexamethasone with a water-in-oil emulsion is effective in treating a murine autoimmune model.
目前针对自身免疫性疾病的治疗方法主要集中在治疗症状上，而不是针对潜在的疾病原因。改善自身免疫治疗的一个主要障碍是缺乏抗原特异性。成功的抗原特异性免疫治疗（ASIT）将允许改善自身免疫性疾病的治疗。在这项工作中，地塞米松与自身抗原（PLP）在体内共同递送来创建有效的 ASIT 以治疗实验性自身免疫性脑脊髓炎（EAE）。使用不完全弗氏佐剂（IFA）乳剂作为共递药载体，发现自身抗原的控制释放对于抑制临床疾病症状很重要。通过细胞因子分析免疫反应表明，地塞米松对于将免疫反应从炎症中转移出来很重要。同时递送自身抗原和地塞米松增加了 B 细胞群体和抗体产生，表明体液免疫反应增强。总体而言，这些数据表明，水包油乳剂共递送 PLP 和地塞米松可有效治疗小鼠自身免疫模型。
