Preventative therapy for post-traumatic osteoarthritis
Compositions comprising a reverse-temperature sensitive hydrogel comprising a biopolymer such as a polysaccharide and a synthetic polymer, and a compound in an amount that reversibly inhibits respiratory enzyme complex I, and methods of using the composition, are provided.
1. An injectable composition comprising a hydrogel comprising hyaluronic acid having a molecular weight of 1 million Da or greater and 15% wt/vol to about 20% wt/vol F127, and an amount of amobarbital or a derivative thereof effective to inhibit post-traumatic osteoarthritis.
2. The composition of claim 1 wherein the hyaluronic acid is present in the composition from about 0.01% (wt/vol) and up to about 2.0% (wt/vol).
3. The composition of claim 1 wherein the hyaluronic acid is present at about 0.2% wt/vol to about 1.0% wt/vol.
4. The composition of claim 1 wherein the hydrogel further comprises N-isopropyl acrylamide polymer, a polysaccharide other than hyaluronic acid, hydroxypropylcellulose, karya gum, guar gum, gellan gum, alginate, ethylhydroxyethylcellulose, poly(ethyleneoxide-b-propylene oxide-b-ethylene oxide), a PLURONICS® polymer, a poly(ethylene glycol)/poly(D,L-lactic acid-co-glycolic acid) block co-polymer, a polyphosphazine, a polyacrylate, a TETRONICS™ polymer, or a polyethylene oxide-polypropylene glycol block copolymer.
5. The composition of claim 1 wherein the derivative comprises pentobarbital, secobarbital, phenobarbital, or barbital.
6. The composition of claim 1 wherein the amount inhibits mitochondrial dysfunction or chondrocyte energy dysfunction.
7. The composition of claim 1 wherein the amobarbital or a derivative thereof scavenges mitochondrial oxidants or prevents their formation, or stimulates glycolytic ATP production.
8. A method to inhibit chondrocyte death and improve chondrocyte function after injury in a mammal, comprising locally administering an effective amount of the composition of claim 1 to an injured joint of a mammal.
9. The method of claim 8 wherein the composition is injected.
10. The method of claim 8 wherein the composition comprises amobarbital, pentobarbital, secobarbital, or phenobarbital.
11. The method of claim 8 wherein the amount inhibits mitochondrial dysfunction or chondrocyte energy dysfunction.
12. The method of claim 8 wherein the administration reduces ROS production in cartilage.
13. The method of claim 8 wherein the administration is within 4 days of the injury.
14. The method of claim 8 wherein the administration is with 12 hours of the injury.
15. The method of claim 8 wherein the administration is with 5 hours of the injury.
16. The method of claim 8 wherein the injury is a knee, hip, ankle or elbow injury.
17. A method to inhibit post-traumatic osteoarthritis in a mammal, comprising locally administering an effective amount of the composition of claim 1 to a mammal at risk of posttraumatic osteoarthritis as a result of injury to cartilage.
18. The method of claim 17 wherein the composition is injected.
19. The method of claim 17 wherein the composition comprises amobarbital, pentobarbital, secobarbital, or phenobarbital.
20. The method of claim 17 wherein the administration is within 4 days of the injury.
21. The method of claim 17 wherein the mammal has an injured joint.
22. The method of claim 17 wherein the administration is with 12 hours of the injury.
23. The method of claim 17 wherein the administration is with 5 hours of the injury.
24. The method of claim 17 wherein the injury is a knee, hip, ankle or elbow injury.
25. The method of claim 17 wherein the mammal is a human.