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Ultrasound-triggered noninvasive regulation of blood glucose levels using microgels integrated with insulin nanocapsules

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Abstract

Diabetes is a serious public health problem affecting 422 million people worldwide. Traditional diabetes management often requires multiple daily insulin injections, associated with pain and inadequate glycemia control. Herein, we have developed an ultrasound-triggered insulin delivery system capable of pulsatile insulin release that can provide both long-term sustained and fast on-demand responses. In this system, insulin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocapsules are encapsulated within chitosan microgels. The encapsulated insulin in nanocapsules can passively diffuse from the nanoparticle but remain restricted within the microgel. Upon ultrasound treatment, the stored insulin in microgels can be rapidly released to regulate blood glucose levels. In a chemically-induced type 1 diabetic mouse model, we demonstrated that this system, when activated by 30 s ultrasound administration, could effectively achieve glycemic control for up to one week in a noninvasive, localized, and pulsatile manner.

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Acknowledgements

This work was supported by the Junior Faculty Award of the American Diabetes Association (ADA), the NC State Faculty Research and Professional Development Award to Z. G. The authors thank Dr. John Buse at UNC-CH for helpful discussion and Dr. Elizabeth Loboa, Dr. Michael Gamcsik and Dr. Glenn Walker for assistance in equipment usage.

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Authors and Affiliations

  1. Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC, 27695, USA

    Jin Di, Jicheng Yu, Yanqi Ye & Zhen Gu

  2. Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Jin Di, Jicheng Yu, Yanqi Ye & Zhen Gu

  3. Department of Chemical and Biological Engineering, Iowa State University, Ames, IA, 50011, USA

    Qun Wang

  4. Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC, 27695, USA

    Shanshan Yao, Dingjie Suo, Matthew Pless, Yong Zhu & Yun Jing

  5. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Zhen Gu

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  1. Jin Di
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  2. Jicheng Yu
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  3. Qun Wang
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  4. Shanshan Yao
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  7. Matthew Pless
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  8. Yong Zhu
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  9. Yun Jing
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  10. Zhen Gu
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Correspondence to Yun Jing or Zhen Gu.

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These authors contributed equally to this work.

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Ultrasound-triggered noninvasive regulation of blood glucose levels using microgels integrated with insulin nanocapsules

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Di, J., Yu, J., Wang, Q. et al. Ultrasound-triggered noninvasive regulation of blood glucose levels using microgels integrated with insulin nanocapsules. Nano Res. 10, 1393–1402 (2017). https://doi.org/10.1007/s12274-017-1500-z

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  • DOI: https://doi.org/10.1007/s12274-017-1500-z

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