Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease
Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease
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DOI：
10.1038/gt.2008.67
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发表时间：
2008-09-01
期刊：
影响因子：
5.1
通讯作者：
Amiji, M. M.
中科院分区：
文献类型：
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作者：
Bhavsar, M. D.;Amiji, M. M.
本研究的目的是探讨口服白细胞介素 10 (IL-10) 基因疗法治疗炎症性肠病 (IBD) 的潜力。微球口腔系统中的纳米颗粒 (NiMOS) 采用 B 型明胶纳米颗粒中表达鼠 IL-10 的质粒 DNA 配制而成，并进一步封装在聚（ε-己内酯）微球基质中。在急性结肠炎模型中口服给药后，通过定量实时 PCR 和 ELISA 测量大肠中 IL-10 的表达。局部表达的IL-10能够抑制促炎细胞因子的水平，例如IFN-γ、TNF-α、IL-1α、IL-1β和IL-12以及某些趋化因子。通过组织组织学分析和髓过氧化物酶活性评估，体重增加、良好的临床活性评分、结肠长度和重量的恢复以及炎症反应的抑制进一步证明了转染的 IL-10 的治疗益处。这项研究的结果为口服基因递送和转染及其在 IBD 治疗中的潜在用途提供了非常令人鼓舞的证据。
The objective of this study was to examine the potential of oral interleukin-10 (IL-10) gene therapy for the treatment of inflammatory bowel disease (IBD). Nanoparticles-in-microsphere oral system (NiMOS) was formulated with murine IL-10-expressing plasmid DNA in type-B gelatin nanoparticles, which were further encapsulated in poly(epsilon-caprolactone) microsphere matrix. Upon oral administration in an acute colitis model, IL-10 expression in the large intestine was measured by quantitative real-time PCR and ELISA. The locally expressed IL-10 was able to suppress the levels of proinflammatory cytokines, such as IFN-gamma, TNF-alpha, IL-1 alpha, IL-1 beta and IL-12, as well as certain chemokines. The therapeutic benefits of transfected IL-10 were further demonstrated by an increase in body weight, favorable clinical activity score, restoration in colon length and weight, and suppression of inflammatory response as assessed by tissue histological analysis and myeloperoxidase activity. The results of this study provide highly encouraging evidence of oral gene delivery and transfection and potential utility in IBD therapy.