Polymer formulations for delivery of bioactive agents
Disclosed in the present application are compositions comprising a bioresorbable polymer matrix and a bio active agent, wherein the bioactive agent is dispersed within polymer matrix as a solid. Also provided herein are methods for preparing a bioactive agent formulation, wherein the agent is present in a solid form and, wherein the agent is occluded into a polymeric matrix by polymerization of polymer matrix precursors or by self assembly of the polymer.
1. A hydrogel composition formed by combining an aqueous buffer, a thiol-functionalized hyaluronic acid and a crosslinking accelerant in the presence of a gel-persistence-enhancing compound selected from the group consisting of N-acetyl cysteine, glutathione, 2,3-dimercapto-1-propanesulfonic acid, 2,3-dimercapto-1-propanesulfonic acid sodium salt monohydrate, cysteine, dihydrolipoic acid, and pharmaceutically acceptable salts thereof, wherein the hydrogel comprises disulfide crosslinks.
2. The composition of claim 1 further comprising an excipient.
3. The composition of claim 1 having a pH of between 5 and 8 when in aqueous solution.
4. The composition of claim 1 , wherein the thiol-functionalized hyaluronic acid has a formula:
wherein:
n≧2;
Y is a residue of the hyaluronic acid; and
L is a substituted or unsubstituted hydrocarbyl group, a substituted or unsubstituted heterohydrocarbyl group, a polyether group, a polyamide group, a polyimino group, an aryl group, a polyester, a polythioether group, a polysaccharyl group or a combination thereof.
5. The composition of claim 1 , wherein the thiol-functionalized hyaluronic acid has a formula:
wherein HA is a residue of hyaluronic acid and n≧2.
6. The composition of claim 1 , where the gel-persistence-enhancing compound is cysteine or a pharmaceutically acceptable salt thereof.
7. The composition of claim 1 , further comprising a bioactive agent as solid particles.
8. The composition of claim 7 , wherein the bioactive agent is a steroid.
9. The composition of claim 8 , wherein the steroid is selected from the group consisting of triamcinolone, triamcinolone diacetate, triamcinolone acetonide, triamcinolone hexacetonide, methylprednisolone and dexamethasone.
10. The composition of claim 8 , wherein the steroid is triamcinolone acetonide.
11. The composition of claim 7 , wherein the solid particles have a particle size between about 0.1 micron and 2 mm.
12. The composition of claim 7 , wherein the bioactive agent is not covalently bound to the thiol-functionalized hyaluronic acid.
13. The composition of claim 1 , which forms in about 1 second to 30 minutes after combining the thiol-functionalized hyaluronic acid, the gel-persistance enhancing compound, and the crosslinking accelerant in aqueous buffer.
14. A kit for providing a hydrogel composition of claim 1 , the kit comprising, in one or more first containers, a thiol-functionalized hyaluronic acid, a gel-persistence enhancing compound as recited in claim 1 , and a crosslinking accelerant, and, in a second containiner, an aqueous buffer.
15. The kit of claim 14 , further comprising in the one or more first containers or in a third container, a steroid selected from the group consisting of triamcinolone, triamcinolone diacetate, triamcinolone hexacetonide, triamcinolone acetonide, methylprednisolone and dexamethasone.
16. A method of treating a medical condition in a mammal in need thereof, the method comprising contacting a tissue site of mammal with the composition of claim 1 .
17. The kit of claim 15 , wherein the steroid is triamcinolone acetonide.
18. The composition of claim 1 , wherein the crosslinking accelerant is an oxidant.
19. The composition of claim 18 , wherein the oxidant is selected from the group consisting of air, molecular iodine, hydrogen peroxide, an alkyl hydroperoxide, a peroxy acid, a dialkyl sulfoxide, a persulfate, Co 3+ , Ce 4+ , a metal oxide and a halogen transfer agent.