Stabilization of glucagon by trehalose glycopolymer nanogels

Patent metadata

Field	Value
Publication number	US-11951176-B2
Application number	US-201816771588-A
Country	US
Kind code	B2
Filing date	Nov 30, 2018
Priority date	Dec 11, 2017
Publication date	Apr 9, 2024
Grant date	Apr 9, 2024

Abstract

Trehalose-based nanogels for stabilizing and controlled releasing biomolecules such as glucagons are disclosed. Specifically, trehalose-based nanogels comprise (a) a copolymer comprising first methacrylate units and second methacrylate units, wherein (i) the first methacrylate units comprise trehalose side chains; and (ii) the second methacrylate units comprise disulfide side chains; (b) dithiol cross-linkers; wherein the dithiol cross-linkers cross link the copolymer through the disulfide side chains of the second methacrylate units.

First claim

The invention claimed is:

1. A trehalose-based nanogel, the nanogel comprising:
(a) a copolymer comprising first units and second units, wherein
(i) the first units comprise trehalose side chains; and
(ii) the second units comprise disulfide side chains; and

(b) dithiol cross-linkers;
wherein the dithiol cross-linkers cross-link the copolymer through the disulfide side chains of the second units; and
wherein the nanogel further comprises one biomolecule covalently bonded with the copolymer,
wherein the biomolecule is used as a cross-linker.

2. The trehalose-based nanogel of claim 1 , wherein
(i) the first units are first methacrylate units comprising the trehalose side chains; and
(ii) the second units are second methacrylate units comprising the disulfide side chains;
wherein the dithiol cross-linkers cross-link the copolymer through the disulfide side chains of the second methacrylate units.

3. The trehalose-based nanogel of claim 2 , wherein the nanogel has an average particle size in the range of 2-500 nm.

4. The trehalose-based nanogel of claim 3 , wherein the nanogel has an average particle size in the range of 6-20 nm.

5. The trehalose-based nanogel of claim 2 , wherein the copolymer has the structure of:

6. The trehalose-based nanogel of claim 1 , wherein the biomolecule is glucagon.

7. The trehalose-based nanogel of claim 1 , wherein the nanogel is biocompatible.

8. The trehalose-based nanogel of claim 1 , wherein the biomolecule is controlled-releasable.

9. A Glucagon-containing nanogel, the nanogel comprising a trehalose-based copolymer comprising:
a) a methacrylate-based backbone;
b) at least one trehalose-based side chain;
c) at least one disulfide side chain; and
d) glucagons;
wherein the glucagons are chemically modified to include more than one thiol and the glucagons cross link the disulfide side chains of the nanogel.

10. The Glucagon-containing nanogel of claim 9 , wherein the nanogel has an average particle size in the range of 2-500 nm.

11. The Glucagon-containing nanogel of claim 10 , wherein the nanogel has an average particle size in the range of 6-20 nm.

12. The Glucagon-containing nanogel of claim 9 , wherein the nanogel is biocompatible.

13. The Glucagon-containing nanogel of claim 9 , wherein the glucagons are controlled-releasable.

14. The Glucagon-containing nanogel of claim 9 , wherein the trehalose-based copolymer comprises:

15. A method of making glucagon-containing nanogels, comprising the steps of:
a) producing a copolymer comprising first methacrylate units and second methacrylate units, wherein the first methacrylate units comprise trehalose side chains; and the second methacrylate units comprise disulfide side chains;
b) reacting glucagon with a thiolating agent to produce modified glucagon having more than one thiol; and
c) conjugating the modified glucagon into the co-polymer to form glucagon-containing nanogels.

16. The method of claim 15 , wherein the nanogel has an average particle size in the range of 2-500 nm.

17. The method of claim 15 , wherein the nanogel is biocompatible or the glucagon are controlled-releasable.

Assignees

• Univ California

Inventors

• Maynard Heather D
• Boehnke Natalie

Classifications

• A61K47/6903 Primary

  the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel · CPC title

• A61K47/58

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title

• C07K14/605

  Glucagons · CPC title

• C08F8/34

  Introducing sulfur atoms or sulfur-containing groups · CPC title

• C08F220/282

  and containing two or more oxygen atoms · CPC title