Conjugated lipomers and uses thereof
The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein R 3 and R 4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.
1. A conjugated lipomer of the Formula (II):
A L 1 n Z (II)
or a salt thereof, wherein:
each instance of L 1 is independently formula:
provided that at least one L 1 is formulae (ii), and at least one L 1 is formulae (iii);
n is an integer between 3 and 25, inclusive;
each instance of R 2 is independently hydrogen, a substituted or unsubstituted polyethyleneimine, or a group of the formula (iii′):
each instance of R 3 is independently substituted or unsubstituted C 8-20 alkyl;
each instance of R 4 is hydrogen;
A is —N(R 5 ) 2 , wherein each instance of R 5 is independently hydrogen, or a group of the formula (iii′); and
Z is hydrogen, or a group of the formula (iii′).
2. The conjugated lipomer of claim 1 , or a salt thereof, wherein each instance of L 1 is independently selected from formula (ii) and formula (iii).
3. The conjugated lipomer of claim 1 , or a salt thereof, wherein n is an integer between 5 and 25, inclusive.
4. The conjugated lipomer of claim 1 , or a salt thereof, wherein n is an integer between 10 and 15, inclusive.
5. The conjugated lipomer of claim 1 , or a salt thereof, wherein the conjugated lipomer is prepared from a polyethyleneimine polymer having a number average molecule weight (Mn) of less than 1200 g/mol.
6. The conjugated lipomer of claim 5 , or a salt thereof, wherein the polyethyleneimine polymer has a number average molecule weight (Mn) of about 600 g/mol.
7. The conjugated lipomer of claim 1 , or a salt thereof, wherein each instance of R 2 is independently a substituted or unsubstituted polyethyleneimine, or a group of formula (iii′).
8. The conjugated lipomer of claim 1 , or a salt thereof, wherein each instance of R 3 is independently unsubstituted C 8-20 alkyl.
9. The conjugated lipomer of claim 8 , or a salt thereof, wherein each instance of R 3 is —C 13 H 27 .
10. The conjugated lipomer of claim 1 , or a salt thereof, wherein:
each instance of L 1 is independently selected from formula (ii) and formula (iii);
n is an integer between 10 and 15, inclusive;
each instance of R 2 is independently a substituted polyethyleneimine, or a group of formula (iii′);
R 3 is —C 13 H 27 ;
R 4 is hydrogen;
each R 5 is a group of formula (iii′); and
Z is a group of formula (iii′).
11. A composition comprising the conjugated lipomer of claim 10 , or a salt thereof, and an agent.
12. The composition of claim 11 , wherein the agent is a cardiovascular active agent, a vasoactive agent, or an antihypertensive agent.
13. The composition of claim 11 , wherein the agent is small molecule.
14. The composition of claim 11 , wherein the agent is a polynucleotide.
15. The composition of claim 14 , wherein the polynucleotide is DNA.
16. The composition of claim 14 , wherein the polynucleotide is RNA.
17. The composition of claim 16 , wherein the RNA is RNAi, dsRNA, siRNA, shRNA, miRNA, or antisense RNA, or an RNA that encodes a protein or peptide.
18. The composition of claim 17 , wherein the RNA is siRNA or miRNA.
19. A method of delivering an agent to a subject, comprising administering to the subject an effective amount of the composition of claim 11 .