Granted Patent B2

US 7,312,206 · App. 10/468,652 · Granted Dec 25, 2007

Abstract

Claims (32)

1. A sterol derivative according to general formula (1):

cation-spacer 2−Y−spacer 1−X−sterol  (1),

wherein;

said cation is a nitrogen base selected from the group consisting of piperazines, imidazoles, morpholines, purines, pyrimidines, and pyridines;

said spacers 1 and 2 are independently linear, or branched C 1-8 alkyl, and comprise 0-2 ethylenically unsaturated bonds;

said linking group X is selected from the group consisting of —(C═O)—O— and —(C═O)—NH—;

said linking group Y is selected from the group consisting of —O—(O═C)—, —NH—(O═C)——(C═O)—O—, and —(C═O)—NH—;

said sterol is selected from the group consisting of cholesterol, sitosterol, campesterol, desmosterol, fucosterol, 22-ketosterol, 20-hydroxysterol, stigmasterol, 22-hydroxycholesterol, 25-hydroxycholesterol, lanosterol, 7-dehydrocholesterol, dihydrocholesterol, 19-hydroxycholesterol, 5α-cholest-7-en-3β-ol, 7-hydroxycholesterol, epicholesterol, ergosterol, and dehydroergosterol; and

said sterol derivative has a pKa value of between about 3.5 and about 8.

2. The sterol derivative according to claim 1 , wherein the sterol derivative has a pKa value of between about 4 and about 7.

3. A liposome comprising the sterol derivative of claim 1 .

4. The liposome of claim 3 , wherein said liposome comprises between about 5 mole-% and about 50 mole-% of sterol derivatives.

5. The liposome of claim 4 , wherein said liposome comprises between about 5 mole % and about 40 mole-% of sterol derivatives.

6. The liposome of claim 5 , wherein said liposome comprises between about 10 mole-% and about 30 mole-% of sterol derivatives.

7. The liposome of claim 3 , wherein the liposome comprises one or more lipids secreted from the group consisting of phosphatidyl choline, phosphatidyl ethanolamine, and diacylglycerol.

8. The liposome of claim 7 , wherein said liposome is neutral or negatively charged at a pH of from about 7.0 to about 7.8.

9. The liposome of claim 3 , wherein said liposome has an average size of between about 50 and 1000 nm.

10. The liposome of claim 9 , wherein said liposome has an average size of between about 50 and 300 nm.

11. The liposome of claim 10 , wherein said liposome has an average size of between about 60 and 130 nm.

12. The liposome of claim 3 , wherein said liposome further comprises an active substance.

13. The liposome claim 12 , wherein said active substance is selected from the group consisting of a protein, peptide, a DNA, an RNA, an antisense nucleotide, a decoy nucleotide, and a mixture thereof.

14. The liposome of claim 12 , wherein at least about 80% of said active substance is situated inside the liposome.

15. A method of loading the liposome of claim 12 with an active substance, said method comprising:

encapsulating said active substance in said liposome at a binding pH value; and removing unbound active substances at a second pH value.

16. A method of loading the liposome of claim 12 with an active substance, said method comprising:

permeabilizing said liposome by treatment at a pH value sufficient to enable loading of said active substance and sealing said liposome.

17. A method for tim transport and release of an active substance in a subject. said method comprising administering to said subject the liposome of claim 12 .

18. The method of claim 17 , wherein said administration is intravenous or peritoneal.

19. A transport and release system for the transport and release of an active substance in a subject, said system comprising the liposome of claim 12 .

20. A depot formulation or circulative depot comprising the liposome of claim 12 .

21. A nanocapsule prepared from the liposome of claim 3 .

22. A vector for transfecting cells in vivo, in vitro or ex vivo , said vector comprising the liposome of claim 3 and a nucleic acid.

Assignments (6)