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Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery

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  • Special Issue: Dedicated to the 100th Anniversary of Nankai University
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Abstract

For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insulin delivery system yet could mimic both controlled basal insulin release and rapid prandial insulin release in response to real-time blood glucose changes. Here we reported an artificial insulin delivery system, mimicking physiological basal and prandial insulin secretion, to achieve real-time glycemic control and reduce risk of hypoglycemia. A phenylboronic acid (PBA)/galactosyl-based glucose-responsive insulin delivery system was prepared with insulin-loaded micelles embedded in hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles could swell and achieve rapid glucose-responsive release of insulin, mimicking prandial insulin secretion. When the glucose level returned to the normal state, only the micelles partially responded to glucose and still released insulin gradually. The hydrogel with increased crosslinking density could slow down the diffusion speed of insulin inside, resulting in controlled release of insulin and simulating physiological basal insulin secretion. This hydrogel-micelle composite insulin delivery system could quickly reduce the blood glucose level in a mouse model of type 1 diabetes, and maintain normal blood glucose level without hypoglycemia for about 24 h. This kind of glucose-responsive hydrogel-micelle composite may be a promising candidate for delivery of insulin in the treatment of diabetes.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (51603105, 51773099, 51390483, 91527306, 21620102005) and the Program for Changjiang Scholars and Innovative Research Team in University (IRT1257).

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Authors and Affiliations

  1. State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin, 300071, China

    Juan Lv, Gang Wu, Ying Liu, Chang Li, Yingli An, Rujiang Ma & Linqi Shi

  2. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, China

    Linqi Shi

  3. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China

    Fan Huang, Yumin Zhang & Jinjian Liu

Authors
  1. Juan Lv
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  2. Gang Wu
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  3. Ying Liu
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  4. Chang Li
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  5. Fan Huang
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  6. Yumin Zhang
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  7. Jinjian Liu
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  8. Yingli An
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  9. Rujiang Ma
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  10. Linqi Shi
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Corresponding authors

Correspondence to Rujiang Ma or Linqi Shi.

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11426_2018_9419_MOESM1_ESM.pdf

Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery

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Lv, J., Wu, G., Liu, Y. et al. Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery. Sci. China Chem. 62, 637–648 (2019). https://doi.org/10.1007/s11426-018-9419-3

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  • DOI: https://doi.org/10.1007/s11426-018-9419-3

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