Amine-containing lipidoids and uses thereof
Provided herein are lipidoids that may be prepared from the conjugate addition of alkylamines to acrylates. In some embodiments, provided lipidoids are biodegradable and may be used in a variety of drug delivery systems. Given the amino moiety of the lipidoids, they are well-suited for the delivery of polynucleotides, in addition to other agents. Nanoparticles containing the inventive lipidoids and polynucleotides have been prepared and have been shown to be effective in delivering siRNA.
1. A compound of Formula (I):
or a salt thereof,
wherein
each L is, independently, branched or unbranched C 1-6 alkylene, wherein L is optionally substituted with one or more fluorine radicals;
each R A is, independently, branched or unbranched C 1-6 alkyl, C 3-7 cycloalkyl, or branched or unbranched C 4-12 cycloalkylalkyl, wherein R A is optionally substituted with one or more fluorine radicals;
each R is, independently, hydrogen, or —CH 2 CH 2 C(═O)OR B , provided that at least three R groups are —CH 2 CH 2 C(═O)OR B ;
each R B is, independently, C 10-14 alkyl, wherein R B is optionally substituted with one or more fluorine radicals; and
q is 1, 2, or 3;
provided that the compound is not
2. The compound of claim 1 , wherein the compound is of the Formula (I-a):
or a salt thereof, wherein
each n is, independently, 0, 1, or 2; and
m is 0, 1, or 2.
3. The compound of claim 1 , wherein L is unbranched C 1-6 alkylene.
4. The compound of claim 1 , wherein the compound is of the formula
or a salt thereof.
5. The compound of claim 1 , wherein the compound is of the formula:
or a salt thereof.
6. The compound of claim 1 , wherein all R groups are —CH 2 CH 2 C(═O)OR B .
7. The compound of claim 1 , wherein all R B groups are the same.
8. The compound of claim 1 , wherein R B is C 10 alkyl, C 11 alkyl, C 12 alkyl, C 13 alkyl, or C 14 alkyl.
9. A compound selected from the group consisting of:
and salts thereof.
10. A nanoparticle comprising a compound of claim 1 and one or more agents to be delivered.
11. The nanoparticle of claim 10 , wherein the one or more agents is a polynucleotide, drug, protein, peptide, a small molecule, or gas.
12. A composition comprising one or more compounds of claim 1 , and an excipient.
13. The composition of claim 12 , wherein the composition further comprises an agent selected from the group consisting of an organic molecule, inorganic molecule, nucleic acid, protein, peptide, polynucleotide, targeting agent, an isotopically labeled chemical compound, vaccine, and an immunological agent.
14. A method of administering an agent, the method comprising:
administering to a subject in need thereof a therapeutically effective amount of a composition comprising a compound of claim 1 and an agent to be delivered.
15. The compound of claim 1 , wherein L is ethylene.
16. The compound of claim 1 , wherein L is propylene.
17. The compound of claim 1 , wherein q is 1.
18. The compound of claim 1 , wherein q is 2.
19. The compound of claim 1 , wherein q is 3.
20. The compound of claim 1 , wherein R A is branched or unbranched C 1-6 alkyl.
21. The compound of claim 1 , wherein R A is methyl, ethyl, or propyl.
22. The compound of claim 1 , wherein R A is C 3-7 cycloalkyl.
23. The nanoparticle of claim 11 , wherein the one or more agents is a polynucleotide, and the polynucleotide is RNA.
24. The composition of claim 13 , wherein the agent is a polynucleotide, and the polynucleotide is DNA.
25. The composition of claim 13 , wherein the agent is a polynucleotide, and the polynucleotide is RNA.
26. The composition of claim 25 , wherein the RNA is mRNA, dsRNA, siRNA, shRNA, miRNA, or antisense RNA.
27. The composition of claim 13 , wherein the agent is a polynucleotide, and the polynucleotide encodes a protein or peptide.