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The complexation of insulin with sodium N-[8-(2-hydroxybenzoyl)amino]-caprylate for enhanced oral delivery: Effects of concentration, ratio, and pH

文献类型：期刊论文

作者Weng, Huixian5,6; Hu, Lefei4; Hu, Lei3,5; Zhou, Yihan5,6; Wang, Aohua2,5; Wang, Ning2,5; Li, Wenzhe2,5; Zhu, Chunliu5; Guo, Shiyan5; Yu, Miaorong5
刊名CHINESE CHEMICAL LETTERS
出版日期2022-04-01
卷号33期号:4页码:1889-1894
关键词Oral insulin delivery Permeation enhancer SNAC Absorption mechanism Molecular interaction
ISSN号1001-8417
DOI10.1016/j.cclet.2021.10.023
通讯作者Gan, Yong(ygan@simm.ac.cn)
英文摘要Permeation enhancers (PEs), such as N-[8-(2-hydroxybenzoyl)amino]-caprylate (SNAC), have been reported to improve the oral absorption of various macromolecules. However, the bioavailabilities of these formulations are quite low and variable due to the influences of enzymes, pH and other gastrointestinal barriers. In this study, we revealed that SNAC could interact with insulin to form tight complexes in a specific concentration (insulin >= 40 mu g/mL)-, ratio (SNAC/insulin >= 20:1)- and pH (>= 6.8)-dependent manner, thus contributing to a significantly high efficacy of oral insulin delivery. Specifically, absorption mechanism studies revealed that the SNAC/insulin complexes were internalized into the cells by passive diffusion and remained intact when transported in the cytosol. Furthermore, the complexes accelerated the exocytosis of insulin to the basolateral side, thereby enhancing its intestinal mucosal permeability. Eudragit (R) S100-entrapped SNAC/insulin microspheres were then prepared and exhibited an apparent permeability coefficient (P-app) that was 6.6-fold higher than that of the insulin solution. In diabetic rats, hypoglycemic activity was sustained for more than 10 h after the microspheres were loaded into enteric-coated capsules. Further pharmacokinetic studies revealed an approximately 6.3% oral bioavailability in both the fasted and fed states, indicating a negligible food effect. Collectively, this study provides insight into the interaction between PEs and payloads and presents an SNAC-based oral insulin delivery system that has high oral bioavailability and patient-friendly medication guidance. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
WOS关键词INTESTINAL PERMEATION ENHANCERS ; CHITOSAN NANOPARTICLES ; ABSORPTION ; MACROMOLECULES ; HEPARIN
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000789375500028
出版者ELSEVIER SCIENCE INC
源URL[http://119.78.100.183/handle/2S10ELR8/301004]  
专题新药研究国家重点实验室
通讯作者Gan, Yong
作者单位1.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Beijing 100050, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Univ Sci & Technol China, Nano Sci & Technol Inst, Nanjing 215123, Peoples R China
4.Nanjing Univ Chinese Med, Sch Pharm, Nanjing 210023, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210046, Peoples R China
推荐引用方式
GB/T 7714		 Weng, Huixian,Hu, Lefei,Hu, Lei,et al. The complexation of insulin with sodium N-[8-(2-hydroxybenzoyl)amino]-caprylate for enhanced oral delivery: Effects of concentration, ratio, and pH[J]. CHINESE CHEMICAL LETTERS,2022,33(4):1889-1894.
APA Weng, Huixian.,Hu, Lefei.,Hu, Lei.,Zhou, Yihan.,Wang, Aohua.,...&Gan, Yong.(2022).The complexation of insulin with sodium N-[8-(2-hydroxybenzoyl)amino]-caprylate for enhanced oral delivery: Effects of concentration, ratio, and pH.CHINESE CHEMICAL LETTERS,33(4),1889-1894.
MLA Weng, Huixian,et al."The complexation of insulin with sodium N-[8-(2-hydroxybenzoyl)amino]-caprylate for enhanced oral delivery: Effects of concentration, ratio, and pH".CHINESE CHEMICAL LETTERS 33.4(2022):1889-1894.

入库方式： OAI收割

来源：上海药物研究所

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