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Nano Research 2017, 10(4): 1393-1402 https://doi.org/10.1007/s12274-017-1500-z
Research Article | Issue | Published: 06 March 2017

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

Show Author's Information Jin Di1,2,§,  Jicheng Yu1,2,§,  Qun Wang3,  Shanshan Yao4,  Dingjie Suo4,  Yanqi Ye1,2,  Matthew Pless4,  Yong Zhu4,  Yun Jing4( ),  Zhen Gu1,2,5( )
Joint Department of Biomedical EngineeringUniversity of North Carolina at Chapel Hill and North Carolina State UniversityRaleighNC27695USA
Center for Nanotechnology in Drug Delivery and Division of Molecular PharmaceuticsUNC Eshelman School of PharmacyUniversity of North Carolina at Chapel HillChapel HillNC27599USA
Department of Chemical and Biological EngineeringIowa State UniversityAmesIA50011USA
Department of Mechanical and Aerospace EngineeringNorth Carolina State UniversityRaleighNC27695USA
Department of MedicineUniversity of North Carolina at Chapel HillChapel HillNC27599USA

§ These authors contributed equally to this work.

Keywords:
diabetes, nanocapsule, controlled drug delivery, focused ultrasound, microgel
Cite this article:
Di J, Yu J, Wang Q, et al. Ultrasound-triggered noninvasive regulation of blood glucose levels using microgels integrated with insulin nanocapsules. Nano Research, 2017, 10(4): 1393-1402. https://doi.org/10.1007/s12274-017-1500-z
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Abstract Full text Electronic supplementary material About this article

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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Electronic supplementary material
About this article

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

Show Author's information Jin Di1,2,§, Jicheng Yu1,2,§, Qun Wang3, Shanshan Yao4, Dingjie Suo4, Yanqi Ye1,2, Matthew Pless4, Yong Zhu4, Yun Jing4( ), Zhen Gu1,2,5( )
Joint Department of Biomedical EngineeringUniversity of North Carolina at Chapel Hill and North Carolina State UniversityRaleighNC27695USA
Center for Nanotechnology in Drug Delivery and Division of Molecular PharmaceuticsUNC Eshelman School of PharmacyUniversity of North Carolina at Chapel HillChapel HillNC27599USA
Department of Chemical and Biological EngineeringIowa State UniversityAmesIA50011USA
Department of Mechanical and Aerospace EngineeringNorth Carolina State UniversityRaleighNC27695USA
Department of MedicineUniversity of North Carolina at Chapel HillChapel HillNC27599USA

§ These authors contributed equally to this work.

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.

Keywords: diabetes, nanocapsule, controlled drug delivery, focused ultrasound, microgel

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Publication history
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Acknowledgements

Publication history

Received: 12 December 2016
Revised: 24 January 2017
Accepted: 26 January 2017
Published: 06 March 2017
Issue date: April 2017

Copyright

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2017

Acknowledgements

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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