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 liposome comprising irinotecan and sucrose octasulfate encapsulated within one or more lipids.
2 . The liposome of claim 1 , wherein the liposome comprises one or more lipids and the molar ratio of the irinotecan to the one or more lipids in totality is about 0.02-5.
3 . The liposome of claim 1 , wherein the liposome comprises one or more lipids and has a total of about 0.5 mg irinotecan per mg of total lipid in the liposome.
4 . The liposome of claim 1 , wherein the liposome comprises one or more lipids and has a total of about 0.15 to 1.5 moles of irinotecan per mole of total lipid in the liposome.
5 . The liposome of claim 1 , wherein the liposome comprises one or more lipids and has a ratio of about 0.8 mmol irinotecan per 1 g of total lipid in the liposome.
6 . The liposome of claim 1 , wherein the liposome comprises one or more phospholipids and has a total of about 500 mg irinotecan per mmol of total phospholipid in the liposome.
7 . The liposome of claim 1 , wherein the liposome comprises DSPC and cholesterol.
8 . The liposome of claim 1 , wherein the liposome comprises DSPC, cholesterol and PEG-DSPE in a molar ratio of 3:2:0.015.
9 . The liposome of claim 1 , wherein the liposome is about 110-120 nm.
10 . The liposome of claim 1 , wherein the liposome is further characterized by one or more characteristics selected from the group consisting of:
a. the molar ratio of the irinotecan to the one or more lipids in totality is about 0.02-5;
b. the liposome has a total of about 0.5 mg irinotecan per mg of total lipid in the liposome;
c. the liposome has a total of about 0.15 to 1.5 moles of irinotecan per mole of total lipid in the liposome;
d. the liposome has a ratio of about 0.8 mmol irinotecan per 1 g of total lipid in the liposome;
e. the liposome comprises one or more phospholipids and has a total of about 500 mg irinotecan per mmol of total phospholipid in the liposome;
f. the liposome comprises DSPC and cholesterol;
g. the liposome comprises DSPC, cholesterol and PEG-DSPE in a molar ratio of 3:2:0.015;
h. the liposome is about 110-120 nm; and
i. the liposome comprises about 1.25-2.42 mol irinotecan per g of lipid.
11 . A liposome comprising irinotecan and sucrose octasulfate encapsulated within one or more lipids comprising DSPC and cholesterol in a molar ratio of 3:2.
12 . The liposome of claim 11 , wherein the irinotecan and sucrose octasulfate is encapsulated within a vesicle comprising DSPC, cholesterol and PEG-DSPE in a molar ratio of 3:2:0.015.
13 . The liposome of claim 12 , wherein the liposome is characterized by one or more characteristics selected from the group consisting of:
a. the molar ratio of the irinotecan to the total lipids in the liposome is about 0.02-5;
b. the liposome has a total of about 0.5 mg irinotecan per mg of total lipid in the liposome;
c. the liposome comprises has a total of about 0.15 to 1.5 moles of irinotecan per mole of total lipid in the liposome;
d. the liposome has a ratio of about 0.8 mmol irinotecan per 1 g of total lipid in the liposome; and
e. the liposome comprises one or more phospholipids and has a total of about 500 mg irinotecan per mmol of total phospholipid in the liposome.
14 . The liposome of claim 13 , wherein the liposome is about 110-120 nm.
15 . A pharmaceutical composition comprising an irinotecan liposome pharmaceutical composition to a patient in need thereof, the irinotecan liposome pharmaceutical composition comprising irinotecan and sucrose octasulfate encapsulated in a liposome, wherein at least 90% of the irinotecan in the pharmaceutical composition is encapsulated in liposomes.
16 . The composition of claim 15 , wherein the liposome comprises DSPC, cholesterol and PEG2000-DSPE in a molar ratio of 3:2:0.015, with about 0.15 to 1.5 moles of irinotecan per mole of total lipid in the liposome.
17 . The composition of claim 15 , wherein the liposomes are about 110-120 nm.
18 . The composition of claim 15 , with a total of about 0.5 moles irinotecan per mole of total lipid in the liposome, and a total of about 500 mg irinotecan per mmol total phospholipid in the liposome.
19 . The composition of claim 16 , wherein the liposomes are about 110-120 nm.
20 . The composition of claim 16 , wherein the liposomes comprise a total of about 500 mg irinotecan per mmol total phospholipid in the liposome.