Stabilization of glucagon by trehalose glycopolymer nanogels
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.
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.