Methods and compositions comprising novel cationic lipids
Provided herein are novel cationic lipids, compositions comprising the cationic lipids, and methods of using the cationic lipids. In some claims, the cationic lipids have cytotoxic activity and can be used alone or in combination with a cytotoxic bioactive compound to kill a cell. In some of these claims, the cationic lipid enhances the cytotoxic activity of the cytotoxic bioactive compound. Methods for treating a subject afflicted with a disease or unwanted condition are provided, wherein the method comprises administering a delivery system comprising a novel cationic lipid to the subject. The invention further provides methods for making delivery systems comprising the novel cationic lipids of the invention.
1. A cationic lipid of Formula (I):
wherein:
m and n are each independently integers from 1 to 8;
R 1 and R 2 are each independently —(CH 2 ) p —CH 3 , wherein p is an integer from 8 to 24;
R 3 and R 4 are each independently selected from the group consisting of H, alkyl, and substituted alkyl;
Q 1 and Q 2 are selected from the group consisting of:
wherein at least Q1 or Q2 is:
and pharmaceutically acceptable salts thereof.
2. The cationic lipid of claim 1 , wherein:
m is 2;
n is 4;
p is 13;
R 3 and R 4 are each methyl; and
the cationic lipid of formula (I) is selected from the group consisting of:
3. The cationic lipid of claim 1 , wherein:
m is 2;
n is 3;
p is 17;
R 3 is H;
R 4 is methyl;
the cationic lipid of formula (I) has the following chemical structure:
4. The cationic lipid of claim 1 , wherein:
m is 2;
n is 4;
p is 17;
R 3 and R 4 are each methyl;
the cationic lipid of formula (I) has the following chemical structure:
5. A pharmaceutical composition comprising a cationic lipid of claim 1 and a pharmaceutically acceptable carrier.
6. A delivery system comprising a lipid vehicle and a bioactive compound, wherein said lipid vehicle encapsulates said bioactive compound, and wherein said lipid vehicle comprises a cationic lipid according to claim 1 .
7. A method for delivering a bioactive compound to a cell, said method comprising contacting said cell with the delivery system according to claim 6 .
8. A method for killing a cell, said method comprising contacting said cells with the pharmaceutical composition of claim 5 , wherein the pharmaceutical composition has cytotoxic activity.
9. A method for selectively killing a cell, said method comprising contacting said cell with a targeted delivery system, wherein:
(i) said targeted delivery system comprises a lipid vehicle encapsulating a bioactive compound;
(ii) said lipid vehicle comprises a cationic lipid of claim 1 ;
(iii) said bioactive compound, said cationic lipid, or both have cytotoxic activity; and
(iv) said lipid vehicle comprises an exterior surface comprising a targeting ligand.
10. The method of claim 9 , wherein said bioactive compound comprises a cytotoxic bioactive compound.
11. The method of claim 9 , wherein said targeting ligand comprises anisamide.
12. A method for treating a cancer in a subject, said method comprising administering to said subject the pharmaceutical composition according to claim 5 , wherein said pharmaceutical composition has therapeutic activity against said cancer.
13. The method of claim 12 , wherein said cancer is lung cancer.
14. A method for enhancing the cytotoxic activity of a cytotoxic bioactive compound in a subject, said method comprising administering to said subject the pharmaceutical composition of claim 5 and said cytotoxic bioactive compound.
15. A method for making a cytotoxic polynucleotide delivery system comprising a lipid vehicle encapsulating a polycation and a polynucleotide, said method comprising:
a) mixing a polynucleotide and a polycation, thereby forming a polynucleotide/polycation solution; and
b) mixing a lipid vehicle comprising the cationic lipid according to claim 1 , wherein said cationic lipid has cytotoxic activity, with said polynucleotide/polycation solution, thereby forming said cytotoxic delivery system.
16. The method of claim 15 , wherein said polynucleotide comprises a cytotoxic polynucleotide.
17. The method of claim 15 , wherein step b) produces a lipid vehicle comprising a core supported bilayer.
18. The method of claim 15 , further comprising post-inserting at least one of a lipid-targeting ligand conjugate and a lipid-PEG conjugate into said lipid vehicle, wherein said post-inserting step is performed after forming said delivery system or said polynucleotide delivery system.
19. The method of claim 18 , wherein said lipid-PEG conjugate comprises a 1,2-distearoyl-sn-glycero-S-phosphoethanolamine-N-carboxy-polyethylene glycol 2000 (DSPE-PEG 2000 ).