Lipids for therapeutic agent delivery formulations
The description is directed to ionizable lipids useful for enhancing the delivery of therapeutic agents in liposomes.
1. 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 or C 12-18 alkenyl;
X is —CH 2 — or absent;
L is S—C 1-4 alkylene, —S(O) 2 —C 1-4 alkylene, or
or a pharmaceutically acceptable salt form thereof.
2. The compound of claim 1 , wherein n and m are 1 or 2.
3. The compound of claim 1 , wherein X is absent.
4. The compound of claim 3 , wherein L is
5. The compound of claim 1 , wherein X is —CH 2 .
6. The compound of claim 5 wherein L is —S—C 1-4 alkylene.
7. The compound of claim 6 , wherein L is —S—CH 2 — or —S—CH 2 —CH 2 —.
8. The compound of claim 5 wherein L is —S(O) 2 —C 1-4 alkylene.
9. The compound of claim 8 , wherein L is —S(O) 2 —CH 2 —CH 2 —.
10. The compound of claim 1 , wherein R 1 and R 2 are each C 10-18 alkyl.
11. The compound of claim 1 , wherein R 1 and R 2 are each C 13 alkyl.
12. The compound of claim 1 , wherein R 1 and R 2 are each C 12-18 alkenyl.
13. The compound of claim 1 , wherein R 1 and R 2 are each C 13-17 alkenyl.
14. The compound of claim 1 , wherein R 1 and R 2 are each oleyl or linoleyl.
15. A composition comprising a compound of claim 1 in a lipid nanoparticle comprising a bilayer of lipid molecules.
16. The composition of claim 15 , wherein the compound is 5 to 50 mol % of the lipid molecules.
17. The composition of claim 15 , further comprising a cationic lipid.
18. The composition of claim 17 , wherein the cationic lipid is
19. The composition of claim 17 , wherein the cationic lipid is 5 to 4mol % of the lipid molecules.
20. The composition of claim 17 , wherein the molar ratio of the ionizable lipid and the cationic lipid is about 5:35 to about 35:5.
21. The compound of claim 1 , consisting of a compound with a structure selected from S104, S104-DO, SO2-S104, TU104, TU104-DO, S104-DMO, S104-DLin, TU104-DLin, and T104