LIPOSOMES ENCAPSULATING ADENOSINE
Provided are liposomes that encapsulate adenosine. The liposomes may be formed from sphingomyelin or a combination of sphingomyelin and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or a combination of sphingomyelin and 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) or a combination of sphingomyelin, DMPG, and DMPC. The liposomes encapsulating adenosine may be used to induce cartilage regeneration, treat osteoarthritis, alleviate joint pain, and/or slow, arrest, and/or reverse progressive structural tissue damage associated with osteoarthritis or treat osteoarthritis, rheumatoid arthritis, acute gouty arthritis, and/or synovitis. The liposomes may release adenosine for up to two weeks.
1 . An injectable formulation comprising saline and liposomes comprising one or more lamellae, wherein the liposome lamellae comprise 70 to 100% by mass sphingomyelin and when there is less than 100% by mass sphingomyelin the remainder is 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) or DMPC and DMPG together, wherein the liposomes
(a) have a diameter of 50 nm to 150 µm; and
(b) encapsulate adenosine in the aqueous compartment of the liposome.
2 . The injectable formulation of claim 1 , wherein the concentration of adenosine is 0.1-3 mg/mL.
3 . The injectable formulation of claim 2 , wherein the concentration of adenosine is 0.1 mg/mL.
4 . The injectable formulation of claim 2 , wherein the concentration of adenosine is 0.3 mg/mL.
5 . The injectable formulation of claim 2 , wherein the concentration of adenosine is 3 mg/mL.
6 . The injectable formulation of claim 1 , wherein the adenosine or a portion thereof is released for up to two weeks.
7 . The injectable formulation of claim 1 , further comprising an excipient.
8 . The injectable formulation of claim 1 , wherein the ratio of DMPC and DMPG is from 6:4 to 8:2.
9 . The injectable formulation of claim 8 , wherein the ratio of DMPC and DMPG is 7:3.
10 . The injectable formulation of claim 1 , wherein the total lipid concentration is 7 to 12 mg/mL.
11 . The injectable formulation of claim 1 , wherein one or more of the liposomes have a diameter of 50 nm to 100 µm.
12 . The injectable formulation of claim 6 , wherein one or more of the liposomes have a diameter of 100 nm to 150 µm.
13 . The injectable formulation of claim 1 , wherein the liposomes collapse at a temperature of 35 to 45° C.
14 . The injectable formulation of claim 1 , wherein at least a portion of the adenosine is released within 1 second to 1 hour of administration to a joint of an individual.
15 . The injectable formulation of claim 14 , wherein at least a portion of the adenosine is released within 1 minute to 1 hour of administration to the joint of the individual.
16 . The injectable formulation of claim 15 , wherein at least 1 to 20% of the adenosine is released within 1 minute to 1 hour of administration to the joint of the individual.
17 . The injectable formulation of claim 14 , wherein at least a portion of adenosine or at least 1 to 20% of adenosine is released within 1 second to 10 minutes of administration to the joint of the individual.
18 . The injectable formulation of claim 1 , wherein the liposomes have a diameter of 50 nm to 1 µm.
19 . The injectable formulation of claim 1 , wherein the liposomes have a diameter of 1 µm to 150 µm.
20 . The injectable formulation of claim 1 , wherein the liposome lamellae comprise 75 to 100% by mass sphingomyelin.