Abstract
Self-regulated insulin delivery that mimics native pancreas function has been a long-term goal for diabetes therapies. Two approaches towards this goal are glucose-responsive insulin delivery and islet cell transplantation therapy. Here, biodegradable, partially oxidized alginate carriers for glucose-responsive nanoparticles or islet cells are developed. Material composition and formulation are tuned in each of these contexts to enable glycemic control in diabetic mice. For injectable, glucose-responsive insulin delivery, 0.5 mm 2.5% oxidized alginate microgels facilitate repeat dosing and consistently provide 10 days of glycemic control. For islet cell transplantation, 1.5 mm capsules comprised of a blend of unoxidized and 2.5% oxidized alginate maintain cell viability and glycemic control over a period of more than 2 months while reducing the volume of nondegradable material implanted. These data show the potential of these biodegradable carriers for controlled drug and cell delivery for the treatment of diabetes with limited material accumulation in the event of multiple doses.
| Original language | English (US) |
|---|---|
| Article number | 2201822 |
| Journal | Advanced Healthcare Materials |
| Volume | 12 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 13 2023 |
Funding
M.A.B. and A.L.F. contributed equally to this work. This work was supported by a Leona M. and Harry B. Helmsley Charitable Trust Foundation Grant to D.G.A. and R.L. and the Koch Institute Support (core) Grant P30-CA14051 from the National Cancer Institute at the NIH. L.R.V. and A.L.F. were supported by NSF Graduate Research Fellowships. The authors acknowledge John Martin for providing assistance with GPC, Jennifer Hollister-Lock and Gordon Weir at the Joslin Diabetes Center Islet Isolation Core for providing islets, the Koch Institute Swanson Biotechnology Center for technical support (Animal Imaging & Preclinical Testing Core, Hope Babette Tang (1983) Histology Facility), and Roderick Bronson for assistance with histological analysis. M.A.B. and A.L.F. contributed equally to this work. This work was supported by a Leona M. and Harry B. Helmsley Charitable Trust Foundation Grant to D.G.A. and R.L. and the Koch Institute Support (core) Grant P30‐CA14051 from the National Cancer Institute at the NIH. L.R.V. and A.L.F. were supported by NSF Graduate Research Fellowships. The authors acknowledge John Martin for providing assistance with GPC, Jennifer Hollister‐Lock and Gordon Weir at the Joslin Diabetes Center Islet Isolation Core for providing islets, the Koch Institute Swanson Biotechnology Center for technical support (Animal Imaging & Preclinical Testing Core, Hope Babette Tang (1983) Histology Facility), and Roderick Bronson for assistance with histological analysis.
Keywords
- biomaterials
- glucose-responsive insulin delivery
- islet cell therapy
- oxidized alginate
ASJC Scopus subject areas
- Biomaterials
- Biomedical Engineering
- Pharmaceutical Science
