Liposomes Useful for Drug Delivery
The present invention provides liposome compositions containing substituted ammonium and/or polyanion, and optionally with a desired therapeutic or imaging entity. The present invention also provide methods of making the liposome compositions provided by the present invention.
1 . A pharmaceutical composition comprising irinotecan liposomes, said liposomes encapsulating irinotecan, a polyphosphate having 13-18 phosphate units per polyphosphate molecule and comprising one or more phospholipids, said composition having a mole ratio of irinotecan to lipid between 0.15:1 to 1.5:1.
2 . The composition of claim 1 , wherein the liposomes comprise one or more lipids comprising a lecithin and cholesterol.
3 . The composition of claim 2 , wherein the lecithin and cholesterol are in a 3:2 mole ratio.
4 . The composition of claim 1 , wherein the liposomes comprise one or more lipids comprising DSPC and cholesterol in a 3:2 mole ratio.
5 . The composition of claim 1 , wherein the liposomes comprise one or more lipids comprising DSPC, cholesterol and an amphipathic polymer comprising a polyethylene glycol-lipid.
6 . The composition of claim 1 , wherein the liposomes comprise a polyethylene glycol phosphatidylethanolamine.
7 . The composition of claim 6 , wherein the polyethylene glycol phosphatidylethanolamine comprises a poly(ethylene glycol) moiety having a molecular weight from about 250 to about 20,000.
8 . The composition of claim 1 , wherein the liposomes comprise one or more lipids comprising DSPC, cholesterol and N-(methoxy- poly(ethylene glycol)-oxycarbonyl)-distearoylphosphatidylethanolamine in a mole ratio of 3:2:0.015.
9 . The composition of claim 1 , wherein the liposomes comprise one or more lipids comprising DSPC, cholesterol and methoxy-PEG(2000)-DSPE in a mole ratio of 3:2:0.015.
10 . The composition of claim 1 , wherein the liposomes have a mean size of 112±15.5 nm measured by QELS.
11 . A liposomal irinotecan pharmaceutical composition comprising a dispersion of irinotecan liposomes having a mean size of 112.3±15.5 nm measured by QELS, the irinotecan liposomes encapsulating irinotecan and polyphosphate and comprising one or more phospholipid, the composition having a mole ratio of irinotecan to lipid of 0.15:1 to 1.5:1.
12 . The composition of claim 11 , wherein the liposomes comprise one or more lipids comprising a lecithin and cholesterol and said composition having grams of irinotecan to moles of phospholipid in the ratio of 0.15:1 to 0.55:1.
13 . The composition of claim 11 , wherein the liposomes comprise a lecithin and cholesterol in a 3:2mole ratio.
14 . The composition of claim 11 , wherein the liposomes comprise one or more lipids comprising DSPC, cholesterol and an amphipathic polymer comprising a polyethylene glycol-lipid.
15 . The composition of claim 14 , wherein the polyethylene glycol-lipid comprises a poly(ethylene glycol) having a molecular weight from about 250 to about 20,000.
16 . The composition of claim 11 , wherein the liposomes comprise DSPC, cholesterol and MPEG-2000-DSPE in a mole ratio of 3:2:0.015.
17 . The composition of claim 11 , the composition having a ratio of irinotecan to phospholipid of 200 g per mol phospholipid.
18 . The composition of claim 11 , the composition having a ratio of irinotecan to phospholipid of 300 g per mol phospholipid.
19 . The composition of claim 11 , the composition having a ratio of irinotecan to phospholipid of 400 g per mol phospholipid.
20 . The composition of claim 11 , the composition having a ratio of irinotecan to phospholipid of 500 g per mol phospholipid.
21 . The composition of claim 11 , the composition having a ratio of irinotecan to phospholipid of 550 g per mol phospholipid.
22 . A liposomal irinotecan pharmaceutical composition comprising a dispersion of irinotecan liposomes having a mean size of 112.3±15.5 nm measured by QELS, the irinotecan liposomes comprising cholesterol, a PEGylated lipid, one or more lipids comprising at least one phospholipid, said liposomes encapsulating irinotecan and polyphosphate, the composition having 465.6±26.5 mg irinotecan per mmol phospholipid.
23 . The composition of claim 22 , wherein the liposomes comprise DSPC, and cholesterol in a mole ratio of 3:2.
24 . The composition of claim 22 , wherein the liposomes comprise DSPC, cholesterol and MPEG-2000-DSPE in a mole ratio of 3:2:0.015.