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Microneedle-array patch with pH-sensitive formulation for glucose-responsive insulin delivery

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Abstract

Glucose-responsive insulin delivery systems show great promise to improve therapeutic outcomes and quality of life for people with diabetes. Herein, a new microneedle-array patch containing pH-sensitive insulin-loaded nanoparticles (NPs) (SNP(I)) together with glucose oxidase (GOx)- and catalase (CAT)-loaded pH-insensitive NPs (iSNP(G+C)) is constructed for transcutaneous glucose-responsive insulin delivery. SNP(I) are prepared via double emulsion from a pH-sensitive amphiphilic block copolymer, and undergo rapid dissociation to promote insulin release at a mild acidic environment induced by GOx in iSNP(G+C) under hyperglycemic conditions. CAT in iSNP(G+C) can further consume excess H2O2 generated during GOx oxidation, and thus reduce the risk of inflammation toward the normal skin. The in vivo study on type 1 diabetic mice demonstrates that the platform can effectively regulate blood glucose levels within normal ranges for a prolonged period.

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Acknowledgements

This work was supported by National Key R&D Program of China (No. 2017YFA0205600), National Natural Science Foundation of China (Nos. 31771091 and 51922043), Guangdong Natural Science Funds for Distinguished Young Scholar (No. 2017A030306018), Guangdong Provincial Programs (Nos. 2017ZT07S054 and 2017GC010304), Outstanding Scholar Program of Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) (No. 2018GZR110102001), Guangdong Natural Science Foundation (No. 2018A030310285), Science and Technology Program of Guangzhou (Nos. 201902020018, 201804020060, and 201904010398), and Fundamental Research Funds for Central Universities, National Science Foundation (No. 1919285) and American Diabetes Association (No. 1-15-ACE-21).

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  1. Feng-Qin Luo and Guojun Chen contributed equally to this work.

Authors and Affiliations

  1. Guangzhou First People’s Hospital, and Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, 510006, China

    Feng-Qin Luo, Jia-Xian Li & Jin-Zhi Du

  2. Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, 90095-1413, USA

    Guojun Chen, Daojia Zhou & Zhen Gu

  3. School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510006, China

    Wei Xu, Yong-Cong Huang & Jin-Zhi Du

  4. Department of Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China

    Run Lin

  5. National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, Key Laboratory of Biomedical Engineering of Guangdong Province, Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, China

    Jin-Zhi Du

  6. Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510005, China

    Jin-Zhi Du

  7. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Zhen Gu

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  1. Feng-Qin Luo
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Correspondence to Run Lin, Zhen Gu or Jin-Zhi Du.

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Luo, FQ., Chen, G., Xu, W. et al. Microneedle-array patch with pH-sensitive formulation for glucose-responsive insulin delivery. Nano Res. 14, 2689–2696 (2021). https://doi.org/10.1007/s12274-020-3273-z

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