Injectable Nano-Network for Glucose-Mediated Insulin Delivery
Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial “closed-loop” system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and healt...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/91254 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0003-4255-0492 |
| _version_ | 1811095599528804352 |
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| author | Gu, Zhen Aimetti, Alex A. Wang, Qun Dang, Tram T. Zhang, Yunlong Veiseh, Omid Cheng, Hao Anderson, Daniel Griffith Langer, Robert S |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Gu, Zhen Aimetti, Alex A. Wang, Qun Dang, Tram T. Zhang, Yunlong Veiseh, Omid Cheng, Hao Anderson, Daniel Griffith Langer, Robert S |
| author_sort | Gu, Zhen |
| collection | MIT |
| description | Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial “closed-loop” system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days. |
| first_indexed | 2024-09-23T16:20:31Z |
| format | Article |
| id | mit-1721.1/91254 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:20:31Z |
| publishDate | 2014 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/912542022-09-29T19:35:24Z Injectable Nano-Network for Glucose-Mediated Insulin Delivery Gu, Zhen Aimetti, Alex A. Wang, Qun Dang, Tram T. Zhang, Yunlong Veiseh, Omid Cheng, Hao Anderson, Daniel Griffith Langer, Robert S Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Gu, Zhen Aimetti, Alex A. Wang, Qun Dang, Tram T. Zhang, Yunlong Veiseh, Omid Cheng, Hao Langer, Robert Anderson, Daniel Griffith Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial “closed-loop” system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days. Leona M. and Harry B. Helmsley Charitable Trust (Grant 09PG-T1D027) Tayebati Family Foundation 2014-10-31T17:44:12Z 2014-10-31T17:44:12Z 2013-05 2013-02 Article http://purl.org/eprint/type/JournalArticle 1936-0851 1936-086X http://hdl.handle.net/1721.1/91254 Gu, Zhen, Alex A. Aimetti, Qun Wang, Tram T. Dang, Yunlong Zhang, Omid Veiseh, Hao Cheng, Robert S. Langer, and Daniel G. Anderson. “Injectable Nano-Network for Glucose-Mediated Insulin Delivery.” ACS Nano 7, no. 5 (May 28, 2013): 4194–4201. © 2013 American Chemical Society. https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1021/nn400630x ACS Nano application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Gu, Zhen Aimetti, Alex A. Wang, Qun Dang, Tram T. Zhang, Yunlong Veiseh, Omid Cheng, Hao Anderson, Daniel Griffith Langer, Robert S Injectable Nano-Network for Glucose-Mediated Insulin Delivery |
| title | Injectable Nano-Network for Glucose-Mediated Insulin Delivery |
| title_full | Injectable Nano-Network for Glucose-Mediated Insulin Delivery |
| title_fullStr | Injectable Nano-Network for Glucose-Mediated Insulin Delivery |
| title_full_unstemmed | Injectable Nano-Network for Glucose-Mediated Insulin Delivery |
| title_short | Injectable Nano-Network for Glucose-Mediated Insulin Delivery |
| title_sort | injectable nano network for glucose mediated insulin delivery |
| url | http://hdl.handle.net/1721.1/91254 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0003-4255-0492 |
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