Lipids for therapeutic agent delivery formulations
The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.
1. A composition comprising lipid molecules comprising an ionizable lipid compound of formula I:
wherein
n and m are independently 1, 2, 3, or 4;
R 1 and R 2 are independently C 10-18 alkyl-;
X is —CH 2 —, wherein L is —OC 1-4 alkylene- or
—OC(O)C 1-4 alkylene-; or
X is absent, wherein L is —C 1 alkylene-, —C 3 alkylene-, —C 4 alkylene-, —OC 1-4 alkylene-, or —OC(O)C 1-4 alkylene-; or
X is O or N, wherein L is —C 1-4 alkylene-, or
—C(O)C 1-4 alkylene-;
or a pharmaceutically acceptable salt form thereof;
and a cationic lipid, wherein the cationic lipid is
2. The composition of claim 1 , comprising the compound of formula I, wherein n and m are 1 or 2.
3. The composition of claim 1 , comprising the compound of formula I, wherein X is absent.
4. The composition compound of claim 3 , comprising the compound of formula I, wherein L is —OC 1-4 alkylene-, or —OC(O)C 1-4 alkylene-.
5. The composition of claim 3 , comprising the compound of formula I, wherein L is —CH 2 —, —CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 —.
6. The composition of claim 1 , comprising the compound of formula I, wherein X is —CH 2 —.
7. The composition of claim 6 , comprising the compound of formula I, wherein L is —OC 1-4 alkylene-.
8. The composition of claim 7 , comprising the compound of formula I, wherein L is —OCH 2 CH 2 — or —OCH 2 CH 2 CH 2 —.
9. The composition of claim 6 , comprising the compound of formula I, wherein L is —OC(O)C 1-4 alkylene-.
10. The composition of claim 9 , comprising the compound of formula I, wherein L is —OC(O)CH 2 CH 2 CH 2 —.
11. The composition of claim 1 , comprising the compound of formula I, wherein X is O.
12. The composition of claim 1 , comprising the compound of formula I, wherein R 1 and R 2 are each C 10-18 alkyl-.
13. The composition of claim 12 , comprising the compound of formula I, wherein R 1 and R 2 are each C 13 alkyl-.
14. A composition comprising a compound selected from the group consisting of
or a pharmaceutically acceptable salt form thereof;
and a cationic lipid, wherein the cationic lipid is
15. The composition of claim 1 , wherein the ionizable lipid compound is 5 to 50 mol % of the total lipid molecules.
16. A composition comprising lipid molecules comprising an ionizable lipid compound of formula I:
wherein
n and m are independently 1, 2, 3, or 4;
R 1 and R 2 are independently C 10-18 alkyl-;
X is absent;
L is —CH 2 CH 2 —;
or a pharmaceutically acceptable salt form thereof;
and a cationic lipid, wherein the cationic lipid is
17. The composition of claim 16 , wherein the ionizable lipid compound of formula I consists of
18. A composition comprising lipid molecules comprising an ionizable lipid compound of formula I:
wherein
n and m are independently 2, 3, or 4;
R 1 and R 2 are independently C 12-18 alkenyl-;
X is absent;
L is —CH 2 CH 2 —;
or a pharmaceutically acceptable salt form thereof;
and a cationic lipid, wherein the cationic lipid is
19. A composition comprising lipid molecules comprising an ionizable lipid compound of formula I:
wherein
n and m are independently 2, 3, or 4;
R 1 and R 2 independently are a C 12-18 alkenyl-;
X is —CH 2 —, wherein L is —OC 1-4 alkylene or —OC(O)C 1-4 alkylene-; or
X is absent, wherein L is C 1 -C 4 alkylene, —OC 1-4 alkylene, or
—OC(O)C 1-4 alkylene-; or
X is O or N, wherein L is —C 1-4 alkylene-, or
—C(O)C 1-4 alkylene-;
or a pharmaceutically acceptable salt form thereof;
and a cationic lipid, wherein the cationic lipid is
20. The composition of claim 19 , wherein the ionizable lipid compound of formula I consists of i-Pr-DODC
21. A composition comprising lipid molecules comprising an ionizable lipid compound of formula I:
wherein
n and m are 1;
R 1 and R 2 independently are a C 12-18 alkenyl;
X is —CH 2 —, wherein L is —OC 1-4 alkylene- or —OC(O)C 1-4 alkylene-; or
X is absent, wherein L is —C 1-4 alkylene-, —OC 1-4 alkylene-, or —OC(O)C 1-4 alkylene-; or
X is O or N, wherein L is —C 1-4 alkylene-, or
—C(O)C 1-4 alkylene-;
or a pharmaceutically acceptable salt form thereof;
and a cationic lipid, wherein the cationic lipid is
22. The composition of claim 21 , wherein the ionizable lipid compound of formula I consists of C104-DO