Microgel encapsulated nanoparticles for glucose-responsive insulin delivery
Name
final submitted - Microgel encapsulated nanoparticles for glucose-responsive insulin delivery.pdf
Description
Accepted version
Size
1.18 MB
Format
Adobe PDF
Checksum (MD5)
3d3a92ab68d53e10d817333ad96299c4
Author(s)
Volpatti, Lisa R
Facklam, Amanda L.
Cortinas, Abel Bryan
Lu, Yen-Chun
Matranga, Morgan A.
MacIsaac, Corina
Hill, Michael C.
Langer, Robert S
Anderson, Daniel Griffith
Date Issued
November 2020
Journal
Biomaterials
Publisher
Elsevier BV
Citation
Volpatti, Lisa R. et al. "Microgel encapsulated nanoparticles for glucose-responsive insulin delivery." Biomaterials 267 (January 2021): 120458. © 2020
Version
Author's final manuscript
Abstract
An insulin delivery system that self-regulates blood glucose levels has the potential to limit hypoglycemic events and improve glycemic control. Glucose-responsive insulin delivery systems have been developed by coupling glucose oxidase with a stimuli-responsive biomaterial. However, the challenge of achieving desirable release kinetics (i.e., insulin release within minutes after glucose elevation and duration of release on the order of weeks) still remains. Here, we develop a glucose-responsive delivery system using encapsulated glucose-responsive, acetalated-dextran nanoparticles in porous alginate microgels. The nanoparticles respond rapidly to changes in glucose concentrations while the microgels provide them with protection and stability, allowing for extended glucose-responsive insulin release. This system reduces blood sugar in a diabetic mouse model at a rate similar to naked insulin and responds to a glucose challenge 3 days after administration similarly to a healthy animal. With 2 doses of microgels containing 60 IU/kg insulin each, we are able to achieve extended glycemic control in diabetic mice for 22 days.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.biomaterials.2020.120458
