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 suitable for intra-articular injection comprising saline and liposomes comprising one or more lamellae, wherein the liposome lamellae consist of 70 to 99.9% by mass sphingomyelin, a sterol, 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG), and optionally 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and
(a) the liposomes have a diameter of 50 nm to 150 μm and
(b) the liposomes encapsulate adenosine in the aqueous compartment of the liposome; and
the total concentration of adenosine of the formulation is 1 to 3 mg/mL.
2 . The injectable formulation according to claim 1 , wherein the liposomes have a diameter of about 1 to 100 μm.
3 . The injectable formulation according to claim 1 , wherein the adenosine or a portion thereof is released for up to two weeks.
4 . The injectable formulation according to claim 1 , further comprising an excipient.
5 . The injectable formulation according to claim 1 , wherein DMPC is present and the ratio of DMPC and DMPG is 7:3.
6 . The injectable formulation according to claim 1 , wherein the total lipid concentration is 7 to 200 mg/mL.
7 . The injectable formulation according to claim 1 , wherein one or more of the liposomes have a diameter of 50 nm to 250 nm.
8 . The injectable formulation according to claim 7 , wherein the liposomes are unilamellar.
9 . The injectable formulation according to claim 1 , wherein the liposomes have been prepared via extrusion.
10 . The injectable formulation of claim 1 , wherein the sterol is cholesterol.
11 . The injectable formulation of claim 1 , wherein DMPC is present and the ratio of DMPC to DMPG is 6:4 to 8:2.
12 . A method of i) inducing cartilage regeneration and/or ii) alleviating joint pain and/or inflammation and/or iii) slowing and/or arresting and/or reversing progressive structural tissue damage comprising administering to an individual a therapeutically effective amount of an injectable formulation according to claim 1 , wherein i) cartilage regeneration is induced and/or ii) joint pain and/or inflammation is alleviated or partially alleviated and/or iii) progressive structural tissue damage is slowed or partially slowed and/or arrested or partially arrested and/or is reversed or partially reversed.
13 . The method according to claim 12 , wherein the injectable formulation is administered via intra-articular injection to a joint of the individual and/or is administered in one or more injections.
14 . The method according to claim 12 , wherein the individual has osteoarthritis, rheumatoid arthritis, acute gouty arthritis, and/or synovitis.