Stimuli-responsive systems for controlled drug delivery
A method of delivering a therapeutic agent by providing a cross-linked polymer encapsulating the therapeutic agent to a site in a patient. The degradation rate of the cross-linked polymer is correlated with a local concentration of an indicator, and the therapeutic agent is released as the cross-linked polymer degrades.
1. A material for delivery of insulin in response to glucose, comprising:
conjugates that include insulin covalently linked to a polymer, wherein the polymer includes two or more glucose analogs; and
concanavalin A molecules that cross-link conjugates by non-covalently interacting with glucose analogs on different conjugates,
wherein:
the material is insoluble in the absence of glucose; and
conjugates are released from the material in the presence of glucose at a rate that varies within physiological concentrations of glucose.
2. The material of claim 1 , wherein the two or more glucose analogs include a glucose residue.
3. The material of claim 1 , wherein the two or more glucose analogs include a mannose residue.
4. The material of claim 1 , wherein the two or more glucose analogs include a glucose residue and a mannose residue.
5. The material of claim 1 , wherein the two or more glucose analogs include a glucosamine residue.
6. The material of claim 1 , wherein the two or more glucose analogs include a mannosamine residue.
7. The material of claim 1 , wherein the concanavalin A molecules are chemically modified.
8. The material of claim 1 , wherein the concanavalin A molecules are pegylated.
9. The material of claim 1 , wherein the polymer is a polysaccharide.
10. The material of claim 1 , wherein the polymer is selected from the group consisting of carboxylated polysaccharides, —NH 2 pendant polysaccharides, hydroxylated polysaccharides, alginate, collagen-glycosaminoglycan, collagen, dextran, pullulan, mannan, amylose, amylopectin, glycogen, cellulose, hyaluronate, chondroitin, dextrin, chitosan, co-polymers of the above, adducts of the above, and mixtures of the above.
11. The material of claim 1 , wherein the material is comprised of a plurality of particles.
12. The material of claim 11 , wherein the particles have a size from about 100 nm to about 300 nm.
13. The material of claim 11 , wherein the particles have a size from about 300 nm to about 500 nm.
14. The material of claim 11 , wherein the particles have a size from about 500 nm to about 5 μm.
15. The material of claim 11 , wherein the particles have a size from about 5 μm to about 50 μm.
16. The material of claim 11 , wherein the particles have a size from about 50 μm to about 100 μm.
17. The material of claim 1 , wherein the two or more glucose analogs are each portions of a side group of the polymer.
18. The material of claim 1 , wherein the polymer is derivatized with the two or more glucose analogs.
19. The material of claim 1 , wherein the two or more glucose analogs are incorporated into the backbone of the polymer.
20. A method comprising administering a material of claim 1 to a patient in need thereof.