合成粘液生物材料可在炎症性肠病中提供局部治疗抗体
Taj Yeruva1, Sydney Yang1, Michele Kaluzienski1
1Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
bioRxiv : the preprint server for biology
|September 2, 2025
概括
这项研究引入了一种基于粘素的新型水凝,用于针对炎症性肠病 (IBD) 提供抗TNF-α抗体. 这种局部方法可以增强抗体的吸收和治疗效果,同时最大限度地减少全身副作用.
科学领域:
- 生物材料科学
- 胃肠病学
- 免疫学
背景情况:
- 炎症性肠病 (IBD) 需要慢性治疗,通常使用抗TNF-α单克隆抗体 (mAbs).
- 这些mAbs的系统输送会导致免疫抑制和弱准等副作用.
- 需要本地化药物输送系统来提高IBD治疗的有效性和安全性.
研究的目的:
- 开发和评估一种基于粘素的合成水凝,用于在IBD中局部传递向TNF-α的mAbs.
- 评估这些水凝的生物相容性,药物释放动力学和治疗潜力.
- 为了比较水凝输送的mAbs与系统输送的mAbs的体内表现.
主要方法:
- 通过与4臂PEG- thiol交叉连接,制造出基于粘素的合成水凝.
- 在模拟的胃肠道条件下,水凝中含有抗TNF-α mAbs,并测试了细胞相容性和抗体释放.
- 在体外研究中使用LPS刺激的巨细胞来评估水凝和mAb的生物活性.
- 在体内研究中使用TNBS诱导的大肠炎小鼠来评估通过阴道注射的生物分布和治疗疗效.
主要成果:
- 基于粘素的水凝具有细胞相容性,并以持续的方式释放全长的IgG抗体,在蛋白质溶解环境中加速释放.
- 单独的水凝调节了巨细胞的激活,mAb载荷的水凝保留了抗体的生物活性,减少了促炎细胞因子的产生.
- 在体内研究中,与大肠炎模型中的溶液相比,水凝释放的mAbs的吸收和粘附性增强.
- 通过水凝进行局部注射导致治疗效率更高,全身暴露减少.
结论:
- 合成的基于粘素的水凝代表了在IBD中局部提供生物药物的有希望的平台.
- 这种方法可以改善TNF-α的治疗向,增强药物吸收,并最大限度地降低全身免疫抑制.
- 通过优化mAb的输送和疗效,提供一种改善IBD治疗的潜在策略.
相关概念视频
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
230
Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
230
01:29Inflammatory Bowel Disease IV: Pharmacological Management
185
Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
Pharmacologic...
Pharmacologic...
185
01:29Drugs for Treatment of Ulcerative Colitis in IBD
236
Ulcerative colitis is a chronic inflammatory condition primarily affecting the colon and rectum. The primary drugs used in the treatment of ulcerative colitis are aminosalicylates. They exhibit anti-inflammatory and immunosuppressive properties. They modulate inflammatory mediators and inhibit the activity of nuclear factor κB (NF-κB). Aminosalicylates also reduce inflammation by inhibiting prostaglandin and leukotriene production and decreasing neutrophil chemotaxis and superoxide...
236
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids
201
Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2...
201
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
264
Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
264
01:21Inflammatory Bowel Disease V: Surgical Management
206
Surgical interventions for inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, are essential in managing symptoms and addressing complications. The selection of surgical procedures is contingent upon the specific conditions and complications that stem from these illnesses.
Here are some common surgical interventions for IBD:
Here are some common surgical interventions for IBD:
206