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Research Article

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

Feng-Qin Luo1,§, Guojun Chen2,§, Wei Xu3, Daojia Zhou2, Jia-Xian Li1, Yong-Cong Huang3, Run Lin4( ), Zhen Gu2,7( ), Jin-Zhi Du1,3,5,6( )
Guangzhou First People’s Hospital, and Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou 510006, China
Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095-1413, USA
School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, China
Department of Radiology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
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
Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou 510005, China
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China

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

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Graphical Abstract

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.

Keywords

drug deliverydiabetesglucose-responsivepH-sensitivemicroneedle

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Nano Research
Volume 14 Issue 8,
August 2021
Pages 2689-2696
DOI: 10.1007/s12274-020-3273-z
Cite this article:
Luo F-Q, Chen G, Xu W, et al. Microneedle-array patch with pH-sensitive formulation for glucose-responsive insulin delivery. Nano Research, 2021, 14(8): 2689-2696. https://doi.org/10.1007/s12274-020-3273-z
Topics:
Block copolymers GlucoseGlucose sensors Hydrogen peroxideInsulinMammalspH sensors

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Received: 10 October 2020
Revised: 24 November 2020
Accepted: 30 November 2020
Published: 05 January 2021
© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020
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