Therapeutic composition with enhanced endothelium targeting
A composition that includes nanoparticles with binding affinity for platelets, and methods for using this composition to treat vascular disease are disclosed.
1. A composition comprising:
a plurality of nanoparticles comprising:
a first functional group operatively coupled to a surface of a nanoparticle of the plurality of nanoparticles, wherein the first functional group comprises one or more first peptides, and each of which binds a component of platelets; and
a second functional group operatively coupled to a surface of the nanoparticle, wherein the second functional group comprises one or more second peptides, and each of which binds endothelium,
wherein the nanoparticle further comprises a bioactive agent encapsulated within, adhered to a surface of or integrated into the structure of the nanoparticle, and
wherein the bioactive agent is for treating a vascular disease in a patient and does not activate platelets or induce thrombosis.
2. The composition according to claim 1 , wherein the one or more first peptides comprise an antibody fragment that binds a component of platelets.
3. The composition according to claim 1 , wherein the one or more second peptides comprise an antibody fragment that binds endothelium.
4. The composition according to claim 1 , wherein the nanoparticles comprise micelles, liposomes, polymersomes, hydrogel particles or polymer particles.
5. The composition according to claim 1 , wherein the nanoparticle has a maximum linear dimension of 1000 nanometers.
6. The composition according to claim 1 , wherein the bioactive agent is selected from the group consisting of a corticosteroid, everolimus, zotarolimus, sirolimus, a sirolimus derivative, paclitaxel, a bisphosphonate, ApoA1, a mutated ApoA1, ApoA1 milano, an ApoA1 mimetic peptide, an ABC A1 agonist, an anti-inflammatory agent, an anti-proliferative agent, an anti-angiogenic agent, a matrix metalloproteinase inhibitor and a tissue inhibitor of metalloproteinase.
7. The composition according to claim 1 , wherein the nanoparticles comprise a biodegradable or bioerodable material.
8. The composition according to claim 7 , wherein the nanoparticles biodegrade or bioerode within 1.0 second to 100 hours.
9. The composition according to claim 8 , wherein the nanoparticles biodegrade or bioerode within 10.0 seconds to 10 hours.
10. The composition according to claim 9 , wherein the nanoparticles biodegrade or bioerode within 1.0 minute to 1 hour.
11. The composition according to claim 1 , wherein the nanoparticle further comprises a third functional group that binds vascular cell wall components and is operatively coupled to a surface of the nanoparticle, and wherein the third functional group comprises one or more third peptides.
12. The composition according to claim 11 , wherein the one or more third peptides comprise an antibody fragment.
13. The composition according to claim 12 , wherein the antibody fragment is based on an antibody is selected from the group consisting of an anti-elastin, an anti-collagen, an anti-tissue factor, an anti-laminin, or any combination thereof.
14. A method for localizing nanoparticles to a blood vessel wall comprising;
providing a composition according to claim 1 ; and
administering the composition to a blood vessel in a patient.
15. The method according to claim 14 , wherein administering the composition to a vessel in a patient comprises intraarterial delivery.
16. The method according to claim 15 , wherein intraarterial delivery comprises percutaneous transluminal coronary arterial delivery.
17. The method according to claim 15 , wherein intraarterial delivery comprises using a catheter.
18. The composition according to claim 1 , further comprising platelets.
19. The composition according to claim 18 , wherein the platelets are autologous, allogenic or xenogenic.
20. A method for localizing nanoparticles to a blood vessel wall comprising:
providing a composition according to claim 18 ; and
administering the composition to a blood vessel in a patient.
21. The method according to claim 20 , wherein administering the composition to a blood vessel in a patient comprises intraarterial delivery.
22. The method according to claim 21 , wherein intraarterial delivery comprises percutaneous transluminal coronary arterial delivery.
23. The method according to claim 21 , wherein intraarterial delivery comprises using a catheter.