Author:
Jia Xiaohui,Yuan Zhihua,Yang Yuqin,Huang Xuemei,Han Nana,Liu Xiaojing,Lin Xiaoyu,Ma Tao,Xu Bing,Wang Penglong,Lei Haimin
Abstract
Abstract
Background
Oral administration of insulin (INS) could be absorbed into systemic circulation only if the carrier protected it from the hostile gastrointestinal conditions. However, traditional macromolecular carriers have not totally overcome challenges in addressing these biological barriers.
Result
In this study, inspired by small molecule natural products (SMNPs), we demonstrate the multi-functional self-assembly nanoparticles (BA-Al NPs) originating from baicalin (BA) and AlCl3 through coordination bonds and hydrogen bonds. As a novel carrier for oral insulin delivery (INS@BA-Al NPs), it displayed effective capacity in pH stimuli-responsive insulin release, intestinal mucoadhesion and transepithelial absorption enhance. Meanwhile, BA improved the paracellular permeability for insulin absorption, because of its downregulation at both mRNA and protein level on internal tight junction proteins. In vivo experiments exhibited remarkable bioavailability of INS and an ideal glucose homeostasis in the type I diabetic rat model.
Conclusion
This study offers a novel frontier of multi-functional carriers based on SMNPs with self-assembly character and bioactivity, which could be a promising strategy for diabetes therapy.
Graphical Abstract
Funder
National Natural Science Foundation of China
Beijing Municipal Natural Science Foundation
Beijing Nova Program
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences and Peking Union Medical College
Publisher
Springer Science and Business Media LLC
Subject
Pharmaceutical Science,Applied Microbiology and Biotechnology,Biomedical Engineering,Molecular Medicine,Medicine (miscellaneous),Bioengineering
Reference48 articles.
1. World Health Organization. Deafness and hearing loss, 9/3/2021. 2021. https://www.who.int/health-topics/hearing-loss#tab=tab_2.
2. Ogurtsova K, da Rocha FJ, Huang Y, Linnenkamp U, Guariguata L, Cho N, Cavan D, Shaw J, Makaroff L. IDF Diabetes Atlas: global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract. 2017;128:40–50.
3. Zhou X, Wu H, Long R, Wang S, Huang H, Xia Y, Wang P, Lei Y, Cai Y, Cai D, Liu Y. Oral delivery of insulin with intelligent glucose-responsive switch for blood glucose regulation. J Nanobiotechnol. 2020;18(1):96.
4. Xiao Y, Tang Z, Wang J, Liu C, Kong N, Farokhzad OC, Tao W. Oral insulin delivery platforms: strategies to address the biological barriers. Angew Chem Int Ed Engl. 2020;59(45):19787–95.
5. Easa N, Alany R, Carew M, Vangala A. A review of non-invasive insulin delivery systems for diabetes therapy in clinical trials over the past decade. Drug Discovery Today. 2018;11:010.
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