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 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 —, and L is —OC(O)C 1-4 alkylene-; or
X is absent, and L is —OC 1-4 alkylene- or —OC(O)C 1-4 alkylene-; or
X is O or N, and L is —C 1-4 alkylene-;
or a pharmaceutically acceptable salt form thereof.
2. The compound of claim 1 , wherein n and m are independently 1 or 2.
3. The compound of claim 2 , wherein X is absent.
4. The compound of claim 3 , wherein L is —OC 1-4 alkylene- or —OC(O)C 1-4 alkylene-.
5. The compound of claim 1 , wherein X is —CH 2 —.
6. The compound of claim 5 , wherein L is —OC(O)CH 2 CH 2 CH 2 —.
7. The compound of claim 2 , wherein X is O.
8. The compound of claim 2 , wherein R 1 and R 2 are each C 10-18 alkyl-.
9. The compound of claim 2 , wherein R 1 and R 2 are each C 13 alkyl-.
10. A pharmaceutical composition comprising the compound of claim 1 .
11. The pharmaceutical composition of claim 10 comprising a therapeutically effective amount of RNA.
12. A compound selected from the group consisting of
13. A pharmaceutical composition comprising the compound of claim 12 .
14. The pharmaceutical composition of claim 13 comprising a therapeutically effective amount of RNA.
15. A compound selected from the group consisting of
16. A pharmaceutical composition comprising the compound of claim 15 .
17. The pharmaceutical composition of claim 16 comprising a therapeutically effective amount of RNA.