Magnetically Powered Chitosan Milliwheels for Rapid Translation, Barrier Function Rescue, and Delivery of Therapeutic Proteins to the Inflamed Gut Epithelium.
Magnetically Powered Chitosan Milliwheels for Rapid Translation, Barrier Function Rescue, and Delivery of Therapeutic Proteins to the Inflamed Gut Epithelium.
复制标题
DOI：
10.1021/acsomega.3c00886
复制
发表时间：
2023-03-28
期刊：
影响因子：
4.1
通讯作者：
Neeves, Keith B.
中科院分区：
文献类型：
--
作者：
Osmond, Matthew J.;Korthals, Elizabeth;Zimmermann, Coy J.;Roth, Eric J.;Marr, David W. M.;Neeves, Keith B.
炎症性肠病（IBD）是由肠粘膜中单核细胞过度表达肿瘤坏死因子-α（TNF）介导的。静脉注射中和抗TNF抗体可引起全身免疫抑制，多达三分之一的人对治疗无反应。口服抗TNF可以减少不良反应;然而，它受到运输过程中恶劣肠道环境中抗体降解和生物利用度差的阻碍。为了克服这些缺点，我们证明了磁动力水凝胶颗粒，沿沿着粘膜表面滚动，提供降解保护，并维持抗TNF的局部释放。氧化铁颗粒被嵌入交联的壳聚糖水凝胶中，并过筛以产生100-200 μm的颗粒，称为毫轮（m-wheels）。一旦加载抗TNF，这些m轮在1周内释放其有效载荷的10%至80%，其速率取决于交联密度和pH。旋转磁场在m轮上诱导扭矩，导致玻璃和粘液分泌细胞上的滚动速度大于500 μm/s。在携带抗TNF的m-wheels存在下，TNF-激发的肠上皮细胞单层的渗透性被拯救，所述m-wheels既中和了TNF，又在渗漏的细胞连接上产生了不可渗透的补丁。由于能够在粘膜表面上高速平移，直接向发炎上皮提供持续释放，并提供屏障救援，m-wheels展示了递送治疗性蛋白质用于治疗IBD的潜在策略。
Inflammatory bowel disease (IBD) is mediated by an overexpression of tumor necrosis factor-α (TNF) by mononuclear cells in the intestinal mucosa. Intravenous delivery of neutralizing anti-TNF antibodies can cause systemic immunosuppression, and up to one-third of people are non-responsive to treatment. Oral delivery of anti-TNF could reduce adverse effects; however, it is hampered by antibody degradation in the harsh gut environment during transit and poor bioavailability. To overcome these shortcomings, we demonstrate magnetically powered hydrogel particles that roll along mucosal surfaces, provide protection from degradation, and sustain the local release of anti-TNF. Iron oxide particles are embedded into a cross-linked chitosan hydrogel and sieved to produce 100–200 μm particles called milliwheels (m-wheels). Once loaded with anti-TNF, these m-wheels release 10 to 80% of their payload over 1 week at a rate that depends on the cross-linking density and pH. A rotating magnetic field induces a torque on the m-wheels that results in rolling velocities greater than 500 μm/s on glass and mucus-secreting cells. The permeability of the TNF-challenged gut epithelial cell monolayers was rescued in the presence of anti-TNF carrying m-wheels, which both neutralized the TNF and created an impermeable patch over leaky cell junctions. With the ability to translate over mucosal surfaces at high speed, provide sustained release directly to the inflamed epithelium, and provide barrier rescue, m-wheels demonstrate a potential strategy to deliver therapeutic proteins for the treatment of IBD.
登录
查看更多内容
影响因子：
2.9
作者：
Erickson C;Stager M;Riederer M;Payne KA;Krebs M
通讯作者：
Krebs M
DOI：
10.1111/jth.15617
发表时间：
2022-03
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Disharoon D;Trewyn BG;Herson PS;Marr DWM;Neeves KB
通讯作者：
Neeves KB
影响因子：
16.6
作者：
Kirtane AR;Abouzid O;Minahan D;Bensel T;Hill AL;Selinger C;Bershteyn A;Craig M;Mo SS;Mazdiyasni H;Cleveland C;Rogner J;Lee YL;Booth L;Javid F;Wu SJ;Grant T;Bellinger AM;Nikolic B;Hayward A;Wood L;Eckhoff PA;Nowak MA;Langer R;Traverso G
通讯作者：
Traverso G
影响因子：
5.8
作者：
Gan, Quan;Wang, Tao
通讯作者：
Wang, Tao
影响因子：
8
作者：
Harris, M. Scott;Hartman, Deborah;Fox, Barbara S.
通讯作者：
Fox, Barbara S.