Novel method of stabilizing diagnostic and therapeutic compounds in a cationic carrier system

1 . A method of stabilizing a low molecular weight compound in a liposome, wherein said compound is poorly soluble in a lipid membrane and/or has a low permeability across a lipid membrane, comprising:

a) providing said compound, wherein said compound has a net negative charge, or optionally is modified to have a net negative charge;

b) associating the compound of step a) with a cationic amphiphile having a net positive charge and optionally at least one further anionic and/or neutral amphiphile having a net negative and/or neutral charge; and

c) forming a cationic liposome having a positive zeta potential.

2 . The method of claim 1 , wherein step a) comprises modifying a compound with a moiety that has a net negative charge.

3 . The method of claim 2 , wherein modifying comprises

a) covalently linking a negatively charged moiety to said compound;

b) chelating said compound by a negatively charged ligand; or

c) encarcerating said compound within a negatively charged moiety such as a carcerand, calixarene, fullerene, crown or anti-crown ether.

4 . The method of claim 3 , wherein said modifying is reversible.

5 . The method of claim 1 , wherein said compound is a diagnostic agent, a therapeutic agent, or a combination thereof.

6 . The method of claim 5 , wherein said compound is a diagnostic or imaging agent selected from the group consisting of dyes, near-infrared dyes, fluorescent dyes, gold particles, iron oxide particles and other contrast agents including paramagnetic molecules, X-ray attenuating compounds (for CT and X-ray) contrast agents for ultrasound, X-ray emitting isotopes (scintigraphy), and positron-emitting isotopes (PET).

7 . The method of claim 5 , wherein said compound is a drug-selected from the group consisting of an anti-inflammatory drug, an anti-cancer drug, an enzymatic drug, an antibiotic substance, an antioxidant, a hormone drug, an angiogenesis inhibiting agent, a smooth muscle cell-proliferation/migration inhibitor, a platelet aggregation inhibitor, a release inhibitor for a chemical mediator, and a proliferation/migration inhibitor for vascular endothelium.

8 . The method of claim 1 , wherein said cationic amphiphile is lipid with net positive charge, lysolipids with net positive charge or pegylated lipid with a net positive charge.

9 . The method of claim 8 , wherein said cationic amphiphile is a quaternary ammonium compound.

10 . The method of claim 1 , wherein said anionic and/or neutral amphiphile is sterol or lipid.

11 . The method of claim 10 , wherein the neutral amphiphile is diacylphosphatidylcholine.

12 . The method of claim 1 , wherein the liposome formed in step (c) is virtually free of the unmodified compound.

13 . A cationic liposome obtained by a method of claim 1 .

14 . A pharmaceutical composition comprising a pharmaceutically effective amount of the cationic liposome of claim 13 , together with a pharmaceutically acceptable carrier, diluent and/or adjuvant.

15 - 17 . (canceled)

18 . A method of diagnosing, preventing or treating a condition associated with enhanced angiogenic activity comprising administering the cationic liposome of claim 13 to a patient in need thereof.

19 . A method of diagnosing, preventing or treating a condition associated with enhanced angiogenic activity comprising administering the pharmaceutical composition of claim 14 to a patient in need thereof.

20 . A method of claim 18 , wherein the active ingredient of the medicament is present in a negatively charged prodrug form.

21 . A method of claim 19 , wherein the active ingredient of the medicament is present in a negatively charged prodrug form.

22 . A method of claim 20 , wherein the prodrug form is converted to the active drug at a desired target site.

23 . A method of claim 21 , wherein the prodrug form is converted to the active drug at a desired target site.

24 . The method of claim 3 , wherein modifying comprises covalently linking a negatively charged moiety to said compound by an ester, thioester, ether, thioether, amide, amine, carbon-carbon bond or a Schiff Base;

25 . The method of claim 9 , wherein said quaternary ammonium compound is N-(2,3-diacyloxypropyl)-N,N,N-trimethylammonium.

26 . The method of claim 10 , wherein said sterol or lipid is cholesterol, phospholipid, lysolipid, lysophospholipid, sphingolipid or pegylated lipid with a net negative or neutral charge.