题目: | In Situ Polymerization of Zwitterions on Therapeutic Proteins to Enable Their Effective Oral Delivery |
作者: | Huapan Fang1, Linfu Chen1, Zheng Deng1, Yunxuan Gao1, Yang Yang2, Qian Chen1*,and Zhuang Liu1,3* |
单位: | 1Institute of Functional Nano and Soft Materials, Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China 2Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China 3Macao Institute of Materials Science and Engineering, Macau University of Science and Technology, Taipa 999078, China |
摘要: | Oral administration of protein drugs has always been challenging owing to various intestinal barriers. Herein, we developed an efficient oral protein delivery strategy by using in situ polymerization of zwitterions to encapsulate proteins, which were then loaded into enteric coated capsules for oral feeding. After oral administration of such capsules, the enteric coating would be degraded once the capsule enters the intestine, releasing polyzwitterion/protein nanocomplexes. With the help of polyzwitterion modification, such nanocomplexes were able to pass through the mucus and cellular barriers, likely by the proton-assisted amino acid transporter 1 (PAT1) pathway. Such a polyzwitterion-based protein encapsulation strategy could allow for effective oral delivery of different proteins, including bovine serum albumin (BSA), insulin, and antibodies. Using this strategy, the oral bioavailabilities of insulin and immunoglobin G (IgG) were measured to be as high as 16.9% and 12.5%, respectively. Notably, oral feeding of polyzwitterion/insulin capsules could effectively lower the blood glucose level of diabetic animals (mice, rats, and pigs). Moreover, polyzwitterion/antiprogramed death-1 (αPD-1) capsules were able to induce efficient antitumor immune responses, showing significant tumor inhibition effects toward B16F10- and 4T1-tumor bearing mouse models after oral administration. No significant toxic effect was observed for such oral protein formulations in the treated animals. Our work presents a strategy for the efficient oral delivery of protein drugs, including those with large molecular weights (e.g., antibodies) that can hardly be orally delivered using existing technologies. |
影响因子: | 18.027 |
分区情况: | 一区 |
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责任编辑:郭佳