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Sustained release of exendin-4 from tannic acid/Fe (III) nanoparticles prolongs blood glycemic control in a mouse model of type II diabetes.

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机构： [a]School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, Guangzhou 510275, China [b]Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA [c]Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA [d]Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA [e]Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China [f]Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China [g]Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA [h]Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA

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Exendin-4 has been clinically adopted as an effective drug for treating type 2 diabetes (T2D), but its short circulation half-life in the blood requires two injections per day to maintain effective glycemic control. This significantly limits its clinical application. In this study, we developed a tannic acid/exendin-4/Fe3+ ternary nanoparticle system to provide sustained release of exendin-4 in vivo. The formation of these nanoparticles relies on TA/exendin-4 complexation and stabilization through TA-Fe3+ coordination, where the rapid reaction kinetics can benefit from efficient mixing of all three components. Adapting our recently developed flash nanocomplexation (FNC) method, we formulated nanoparticles with high encapsulation efficiency (~ 100%) of exendin-4, high payload capacity, and high degrees of uniformity and stability because the rapid turbulent mixing facilitated a homogeneous distribution of all three components in the complexation process. Intraperitoneal injection in mice showed that exendin-4 released from the nanoparticles had an AUC 7.2-fold higher than the free exendin-4 injection. Efficacy study in a T2D mouse model showed that the optimized formulation achieved a rapid reduction of the blood glucose level to the normal range within <12 h and maintained the same level for 72 h following a single intraperitoneal dose. The blood glucose level was maintained to below the therapeutic level (< 15 mmol/L) for 6 days, and the treatment led to reduced body weight with pathological and functional improvements in the kidney and liver. This tannic acid/exendin-4/Fe3+ ternary nanoparticle system holds translational potential in treating T2D, due to its improved treatment outcomes in terms of extended release of exendin-4, prolonged control of blood glucose level, reduced dosing frequency, and improved pathological indicators. Copyright © 2019 Elsevier B.V. All rights reserved.

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出版当年[2018]版：

大类 | 1 区

医学

小类 | 1 区药学 2 区化学综合

最新[2025]版：

大类 | 1 区

医学

小类 | 1 区药学 2 区化学：综合

第一作者：

第一作者机构： [a]School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, Guangzhou 510275, China [b]Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA [c]Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA

通讯作者：

通讯机构： [a]School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Guangdong Research Center for Functional Biomaterials Engineering and Technology, Sun Yat-sen University, Guangzhou 510275, China [b]Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA [c]Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD 21218, USA [d]Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA [e]Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China [f]Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China [h]Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA [*1]3400 N. Charles Street, Croft Hall 100, Baltimore, MD 21218, USA. [*2]Fengsheng Hall 511, Xingangxi Rd, Guangzhou, Guangdong 510275, China. [*3]100# Shizi Street, Hongshan Rd, Nanjing, Jiangsu, China.

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