Glucose responsive insulin delivery compositions and methods
AssigneeNorth Carolina State University
InventorsZhen GU, Chao WANG
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Abstract
Disclosed herein is a glucose-responsive insulin delivery system based on the interaction between the glucose-modified insulin and glucose transporters (GLUTs) on erythrocytes (or red blood cells, RBCs). After being conjugated with glucose, insulin can efficiently bind to RBC membranes. The binding is reversible in the setting of hyperglycemia, resulting in fast release of insulin and subsequent drop of blood glucose (BG) level in vivo. In some embodiments, the delivery vehicle can include: 1) intravenously injectable polymeric nanoparticles (˜100 nm in diameter) coated with RBC membrane and loaded with glucose-modified insulin and/or 2) painless microneedle (MN) patches loaded with the complex of GLUT and glucose-modified insulin.
Claims21
-35. (canceled)
An insulin delivery system comprising:
- a reservoir;
- a composition housed in the reservoir, the composition comprising a glucose binding structure and a glucose-modified insulin molecule reversibly bound to the glucose binding structure,
- wherein the glucose-modified insulin molecule comprises an insulin moiety conjugated to at least one glucose moiety by at least one linker molecule.
A method of controlling insulin release to a subject using an insulin delivery system, the method comprising:
- housing a glucose binding structure and a glucose-modified insulin molecule within a reservoir of the insulin delivery system, the glucose-modified insulin molecule reversibly bound to the glucose binding structure and comprising an insulin moiety conjugated to at least one glucose moiety by at least one linker molecule;
- creating a fluidic connection between the reservoir and a blood supply of the subject;
- releasing the glucose-modified insulin molecule from the glucose binding structure and into the blood supply as a glucose concentration in the blood supply increases.
A method of controlling glucose levels in a subject, the method comprising;
- administering a therapeutically effective amount of a composition to a subject having diabetes, the composition comprising;
- a glucose-modified insulin molecule comprising an insulin moiety conjugated to at least one glucose moiety by at least one linker molecule, and
- a glucose binding structure,
- wherein the glucose-modified insulin molecule is reversibly bound to the glucose binding structure, and
- wherein the glucose-binding structure releases a portion of the glucose-modified insulin in high glucose conditions.
Dependencies are inferred from the claim text.