Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations
Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations
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超分子纳米制剂显着提高类风湿关节炎的生物功效
DOI：
10.1002/adma.202100098
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发表时间：
2021-03-17
影响因子：
29.4
通讯作者：
Liu, Kai
中科院分区：
文献类型：
--
作者：
Ma, Chao;Li, Bo;Liu, Kai
类风湿关节炎（RA）是一种典型的慢性疼痛综合征的炎症性疾病，由于常用药物如白细胞介素1受体拮抗剂（IL 1 ra）生物利用度差，半衰期有限，一般需要每天1-2次频繁注射给药进行长期治疗。在这里，合理地开发了一种新的策略，以制造纳米制剂，采用基因工程IL 1 ra蛋白复合物，产生超持久的生物功效。使用大鼠模型，结果表明，这些纳米治疗剂在14天的治疗中显着改善了单次皮下给药的药物方案，表明其非凡的生物利用度和超长效药代动力学。具体而言，纳米制剂的半衰期和生物利用度分别提高到30小时和7倍的水平，显著高于其他系统。因此，这种新的策略具有很大的希望，可以有效地提高患者在RA治疗中的依从性，并且可以适用于遭受类似缺点的其他治疗。
As a typical inflammatory disease with chronic pain syndromes, rheumatoid arthritis (RA) generally requires long-term treatment with frequent injection administration at 1-2 times per day, because common medications such as interleukin1 receptor antagonist (IL1ra) have poor bioavailability and very limited half-life residence. Here a novel strategy to fabricate nanotherapeutic formulations employing genetically engineered IL1ra protein complexes, yielding ultralong-lasting bioefficacy is developed rationally. Using rat models, it is shown that these nanotherapeutics significantly improved drug regimen to a single subcutaneous administration in a 14-day therapy, suggesting their extraordinary bioavailability and ultralong-acting pharmacokinetics. Specifically, the half-life and bioavailability of the nanoformulations are boosted to the level of 30 h and by 7 times, respectively, significantly greater than other systems. This new strategy thus holds great promise to potently improve patient compliance in RA therapy, and it can be adapted for other therapies that suffer similar drawbacks.