Stimuli-responsive systems for controlled drug delivery

• US 8,357,400 B2
• Filed: 11/21/2011
• Issued: 01/22/2013
• Est. Priority Date: 12/17/2002
• Status: Active Grant

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Ying, Jackie Y., Zion, Todd C., Zarur, Andrey
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US13/301,049
• Publication Number:
  US 20120107371A1
• Time in Patent Office: 428 Days
• Field of Search: 424/117, 424/178, 424484-490, 424/493
• US Class Current: 424/488
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

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.

Claims

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, —

NH₂ 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 μ

m.

15. The material of claim 11, wherein the particles have a size from about 5 μ

m to about 50 μ

m.

16. The material of claim 11, wherein the particles have a size from about 50 μ

m to about 100 μ

m.

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.