Liposomal formulations comprising dihydrosphingomyelin and methods of use thereof
First Claim
1. A liposomal composition comprising a liposome, wherein said liposome comprises phospholipid and cholesterol at a molar ratio from 75/25 (mol/mol) total phospholipid/cholesterol to 25/75 (mol/mol) total phospholipid/cholesterol, wherein said at least 20% (molar basis) of total phospholipid present in said liposome is dihydrosphingomyelin (DHSM), wherein the interior of said liposome comprises MnSO4 or MgSO4, and wherein said liposome comprises a therapeutic agent.
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Abstract
The present invention includes novel liposomes comprising dihydrosphingomyelin. The invention also includes compositions comprising these liposomes and a therapeutic agent, in addition to methods and kits for delivering a therapeutic agent or treating a disease, e.g., a cancer, using these compositions.
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Citations
18 Claims
- 1. A liposomal composition comprising a liposome, wherein said liposome comprises phospholipid and cholesterol at a molar ratio from 75/25 (mol/mol) total phospholipid/cholesterol to 25/75 (mol/mol) total phospholipid/cholesterol, wherein said at least 20% (molar basis) of total phospholipid present in said liposome is dihydrosphingomyelin (DHSM), wherein the interior of said liposome comprises MnSO4 or MgSO4, and wherein said liposome comprises a therapeutic agent.
- 9. A method of delivering a therapeutic agent to a patient, comprising administering to the patient a pharmaceutical composition comprising a liposome-encapsulated therapeutic agent, wherein said liposome comprises phospholipid and cholesterol at a molar ratio from 75/25 (mol/mol) total phospholipid/cholesterol to 25/75 (mol/mol) total phospholipid/cholesterol, wherein at least 50% (molar basis) of total phospholipid present in said liposome is dihydrosphingomyelin (DHSM), and wherein the interior of said liposome comprises MnSO4 or MgSO4.
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12. A method of treating a cancer in a mammal, comprising administering to the mammal a pharmaceutical composition comprising a liposome-encapsulated therapeutic agent, wherein said liposome comprises phospholipid and cholesterol at a molar ratio from 75/25 (mol/mol) total phospholipid:
- cholesterol to 25/75 (mol/mol) total phospholipid;
cholesterol, wherein at least 50% of total phospholipids present in said liposome is dihydrosphingomyelin (DHSM), and wherein the interior of said liposome comprises MnSO4 or MgSO4. - View Dependent Claims (13, 14)
- cholesterol to 25/75 (mol/mol) total phospholipid;
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15. A method of producing a pharmaceutical composition, comprising loading a liposome comprising phospholipid id and cholesterol at a molar ratio from 75/25 (mol/mol) total phospholipid:
- cholesterol to 25/75 mol/mol total phospholipid;
cholesterol with a therapeutic agent, wherein at least 50% of the total phospholipids present in said liposome is dihydrosphingomyelin (DHSM), and wherein the interior of said liposome comprises MnSO4 or MgSO4. - View Dependent Claims (16)
- cholesterol to 25/75 mol/mol total phospholipid;
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17. A method of loading a therapeutic agent into a liposome comprising:
- incubating a liposome comprising phospholipid and cholesterol at a molar ratio from 75/25 (mol/mol) total phospholipid;
cholesterol to 25/75 (mol/mol) total phospholipid;
cholesterol and having an encapsulated medium comprising MnSO4 or MgSO4, wherein at least 50% of the total phospholipid of the liposome is dihydrosphingomyelin (DHSM), with an external solution comprising said therapeutic agent and an ionophore at a temperature greater than 60°
C. to form a therapeutic agent-loaded liposome.
- incubating a liposome comprising phospholipid and cholesterol at a molar ratio from 75/25 (mol/mol) total phospholipid;
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18. A kit comprising:
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(a) a liposome comprising phospholipid and cholesterol at a molar ratio from 75/25 (mol/mol) total phospholipid;
cholesterol to 25/75 (mol/mol) total phospholipid;
cholesterol, wherein said at least 50% of total phospholipid present in said liposome is dihydrosphingomyelin (DHSM), and wherein the interior of said liposome comprises MnSO4 or MgSO4, and(b) a therapeutic agent.
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Specification