1. Microgel encapsulated nanoparticles for glucose-responsive insulin delivery
- Author
-
Robert Langer, Corina Macisaac, Morgan A. Matranga, Michael C. Hill, Yen-Chun Lu, Daniel G. Anderson, Lisa R. Volpatti, Abel B. Cortinas, Amanda L. Facklam, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biological Engineering, and Harvard--MIT Program in Health Sciences and Technology.
- Subjects
medicine.medical_treatment ,Biophysics ,Insulin delivery ,Nanoparticle ,Blood sugar ,Bioengineering ,02 engineering and technology ,Pharmacology ,Diabetes Mellitus, Experimental ,Biomaterials ,Mice ,03 medical and health sciences ,Drug Delivery Systems ,Diabetes mellitus ,medicine ,Animals ,Insulin ,Glucose oxidase ,030304 developmental biology ,Glycemic ,0303 health sciences ,Microgels ,biology ,Chemistry ,021001 nanoscience & nanotechnology ,medicine.disease ,Glucose ,Mechanics of Materials ,Drug delivery ,Ceramics and Composites ,biology.protein ,Nanoparticles ,0210 nano-technology - 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., National Cancer Institute (Grant P30-CA14051)
- Published
- 2021
- Full Text
- View/download PDF