Delivery system for nucleic acids
α v β 3 Integrin receptor targeting liposomes comprise a cationic amphiphile such as a cationic lipid, a neutral lipid, and a targeting lipid. The targeting lipid includes a non-peptidic α v β 3 integrin antagonist.
1. An α v β 3 integrin receptor targeting liposome comprising
a cationic lipid;
a neutral lipid;
a trivalent targeting lipid having a targeting domain and a hydrophobic domain bound to the targeting domain; and
a nucleic acid complexed with the cationic lipid;
the cationic lipid being present in an amount in the range of about 1 to about 50 mole percent, and said targeting lipid being present in an amount in the range of about 1 to about 20 mole percent, the mole percent values being based on total moles of lipid in the liposome, and the targeting domain including three non-peptidic α v β 3 integrin antagonists represented by formula (II):
wherein in formula (II), R 4 and R 5 are each hydrogen, or together form a covalent bond; Y is —C(O)— or —CH 2 —; Z 2 is —C(O)—R 6 ; —C(O)OR 6 , or SO 2 R 6 ; R 6 is phenyl, substituted-phenyl, pyridyl, benzyl, substituted-benzyl; C 1 -C 4 haloalkyl, C 2 -C 30 alkyl, C 2 -C 30 alkenyl, C 2 -C 30 alkynyl, or cholesteryl; and Het is 2-pyridyl or 2-imidazolyl.
2. The liposome according to claim 1 wherein the α v β 3 integrin antagonist has the formula
3. The liposome according to claim 1 wherein the α v β 3 integrin antagonist has the formula
4. The liposome according to claim 1 wherein the α v β 3 integrin antagonist has the formula
5. The liposome according to claim 1 wherein the α v β 3 integrin antagonist has the formula
6. The liposome according to claim 1 wherein the α v β 3 integrin antagonist has the formula
7. The liposome according to claim 1 wherein the α v β 3 integrin antagonist has the formula