Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Center, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Curr Drug Deliv. 2014;11(1):146-53. doi: 10.2174/156720181101140212170025.
In this study, we examined the in-vivo characteristics of a novel microencapsulated thalidomide formulation in a murine model of experimental Crohn's disease. Crohn's disease was induced with a single intra-colonic injection of 120 mg/kg of bodyweight of 2,5,6-trinitrobenzene sulfonic acid (TNBS) dissolved in 30% ethanol in Balb/c mice. Level of tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), interleukin 6 (IL-6) and nitric oxide (NO) were measured in tissue homogenate. Moreover, myeloperoxidase (MPO) activity was determined to assess the extent of neutrophil infiltration. Dose response study showed that treating the mice with microencapsulated thalidomide (100 mg/kg of bodyweight) for two weeks significantly decreased the degree of intestinal inflammation related to Crohn's disease. Higher and lower doses (0, 25, 50 and 200 mg/kg of bodyweight) did not exhibit comparable effects. The present study validates the success of alginate-poly-L-lysine-alginate (APA) microcapsules containing thalidomide in reducing colonic inflammation, and proposes a potential remedy for Crohn's disease.
在这项研究中，我们在实验性克罗恩病的小鼠模型中研究了一种新型微囊化沙利度胺制剂的体内特征。使用体重 30%乙醇中溶解的 120mg/kg 的 2,5,6-三硝基苯磺酸（TNBS）对 Balb/c 小鼠进行单次结肠内注射，诱导克罗恩病。在组织匀浆中测量肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和一氧化氮（NO）的水平。此外，还测定髓过氧化物酶（MPO）活性以评估中性粒细胞浸润的程度。剂量反应研究表明，用微囊化沙利度胺（100mg/kg 体重）治疗两周可显著降低与克罗恩病相关的肠道炎症程度。较高和较低剂量（0、25、50 和 200mg/kg 体重）则没有显示出类似的效果。本研究证实了含有沙利度胺的藻酸盐-聚赖氨酸-藻酸盐（APA）微胶囊在减轻结肠炎症方面的成功，并为克罗恩病提出了一种潜在的治疗方法。
