文献类型：期刊文献

英文题名：Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations

作者：Ma, Chao[1,2,3];Li, Bo[2];Zhang, Jinrui[2,4];Sun, Yao[2];Li, Jingjing[2];Zhou, Hangcheng[5];Shen, Jianlei[6,7];Gu, Rui[4];Qian, Jiangchao[5];Fan, Chunhai[6,7];Zhang, Hongjie[1,2];Liu, Kai[1,2]

机构：[1]Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China;[2]Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Rare Earth Resource Utilizat, Changchun 130022, Peoples R China;[3]Harvard Univ, Sch Engn & Appl Sci, 29 Oxford St, Cambridge, MA 02138 USA;[4]Jilin Univ, China Japan Union Hosp, Dept Orthoped, Changchun 130033, Peoples R China;[5]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[6]Shanghai Jiao Tong Univ, Sch Chem & Chem Engn, Frontiers Sci Ctr Transformat Mol, Shanghai 200240, Peoples R China;[7]Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Inst Mol Med, Shanghai 200240, Peoples R China

年份：2021

卷号：33

期号：16

外文期刊名：ADVANCED MATERIALS

收录：;EI(收录号：20211210101096);WOS:【SCI-EXPANDED(收录号:WOS:000629789700001)】；

基金：C.M, B.L., and J.Z. contributed equally to this manuscript. This research was supported by the National Key R&D Program of China (2020YFA0908900 and 2018YFA0902600), K. C. Wong Education Foundation (GJTD-2018-09), the National Natural Science Foundation of China (Grant No. 21877104, 21834007, and 22020102003). All the animal experiments in this work were performed in accordance with legal and institutional guidelines and were carried out under ethics, consent and permissions of the Ethical Committee of Care and Use of Laboratory Animals at Jilin University. Sprague-Dawley (SD) female rats (8-week-old) rats were purchased from the Changchun Institute of Biological Products. The human peripheral lymphocytes RPMI1788 were purchased from Bena Cluture Collection Ltd (China). Type II collagen derived from bovine tendons was purchased from Yuanye Biology Ltd (China). Human fibroblast (HFB) cells were purchased from Pcocell Life Science & Technology (China).

语种：英文

外文关键词：biomaterials; protein engineering; nanomedicine; rheumatoid arthritis; nanoformulations

摘要：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.