Modified carbohydrates, compositions comprising the same, and methods of making and using the same
Modified alginates are described herein along with hydrogels comprising the same. A modified alginate may be prepared by reacting alginate and an aromatic compound (e.g., an aromatic amine) and/or pH sensitive compound. The modified alginates, hydrogels, and/or methods described herein may be used to coat and/or encapsulate at least a portion of a bioactive substance, optionally for oral delivery in humans and other animals.
1. A compound comprising at least one unit having a structure of Formula I:
wherein
Y is absent or a C 1 -C 4 alkyl or C 1 -C 4 alkenyl;
R 1 is each independently selected from the group consisting of —H, —OH, —NH 2 , —COOH, —NO 2 , —CN, —Br, —Cl, —F, —C 1 -C 6 alkylhalide, unsubstituted or substituted —C 1 -C 6 alkyl, unsubstituted or substituted —C 1 -C 6 alkenyl, —SO 2 H, —SO 3 H, —COCH 3 , —Si(OH) 3 , —SO 2 NH 2 , —PO(OR′) 2 , and —B(OH) 2 , wherein R′ is unsubstituted or substituted alkyl, alkenyl, alkynyl, or aryl;
n is from 1 to 1,000,000; and
o is 1, 2, 3, 4, or 5,
wherein at least one R 1 is in the para position and is selected from the group consisting of —NH 2 , —COOH, —NO 2 , —CN, —Br, —Cl, —F, —C 1 -C 6 alkylhalide, unsubstituted or substituted —C 1 -C 6 alkyl, unsubstituted or substituted —C 1 -C 6 alkenyl, —SO 2 H, —SO 3 H, —COCH 3 , —Si(OH) 3 , —SO 2 NH 2 , —PO(OR′) 2 , and —B(OH) 2 , and wherein R′ is unsubstituted or substituted alkyl, alkenyl, alkynyl, or aryl, and
wherein the compound is an alginate polymer.
2. A compound comprising at least one unit having a structure of Formula II:
wherein
Y is absent or a C 1 -C 4 alkyl or C 1 -C 4 alkenyl;
R 1 is each independently selected from the group consisting of —H, —OH, —NH 2 , —COOH, —NO 2 , —CN, —Br, —Cl, —F, —C 1 -C 6 alkylhalide, unsubstituted or substituted —C 1 -C 6 alkyl, unsubstituted or substituted —C 1 -C 6 alkenyl, —SO 2 H, —SO 3 H, —COCH 3 , —Si(OH) 3 , —SO 2 NH 2 , —PO(OR′) 2 , and —B(OH) 2 , wherein R′ is unsubstituted or substituted alkyl, alkenyl, alkynyl, or aryl;
n is from 1 to 1,000,000; and
o is 0, 1, 2, 3, 4, or 5, and
wherein the compound is an alginate polymer.
3. The compound of claim 1 , wherein at least one R 1 has a pKa in a range of about 3 to about 6.
4. The compound of claim 1 , wherein the compound comprises at least one pH sensitive functional group.
5. The compound of claim 1 , wherein the compound is prepared by reacting alginate with a reactant.
6. The compound of claim 5 , wherein the alginate is an oxidized alginate.
7. The compound of claim 5 , wherein the reactant is incorporated into the alginate in an amount of about 1% to about 15% of the polysaccharide units of the alginate.
8. The compound of claim 5 , wherein at least 90% of the reactant is chemically bonded to the alginate.
9. A hydrogel comprising the compound of claim 1 , wherein the compound is present in the hydrogel in an amount of about 0.1% to about 10% w/v of the hydrogel.
10. The hydrogel of claim 9 , wherein the hydrogel is cross-linked.
11. The hydrogel of claim 9 , wherein the hydrogel further comprises a bioactive substance.
12. The hydrogel of claim 11 , wherein the bioactive substance is uniformly distributed within the hydrogel.
13. The hydrogel of claim 9 , wherein the hydrogel further comprises a divalent cation in an amount of about 0.1 mmol to about 1 mmol.
14. The hydrogel of claim 9 , wherein the hydrogel has an elastic modulus in a range of 1 kPa to about 20 kPa.
15. The hydrogel of claim 9 , wherein the hydrogel is in the form of a bead, microcapsule, and/or pellet.
16. A method of treating a subject, the method comprising administering the hydrogel of claim 9 to a subject, wherein the hydrogel comprises at least one bioactive substance, thereby treating the subject.
17. A method of increasing the stability and/or shelf life of a bioactive substance, the method comprising providing a hydrogel of claim 9 , wherein the hydrogel comprises at least one bioactive substance, thereby increasing the stability and/or shelf life of the bioactive substance.
18. The compound of claim 2 , wherein o is 5 and each R 1 is —H.
19. The compound of claim 2 , wherein o is 1, 2, 3, 4, or 5 and at least one R 1 is an unsubstituted or substituted C 1 -C 6 alkyl.
20. The compound of claim 2 , wherein o is 1, 2, 3, 4, or 5 and at least one R 1 is —COCH 3 .