Blood Clot-Targeted Nanoparticles

• US 20080247943A1
• Filed: 08/20/2003
• Published: 10/09/2008
• Est. Priority Date: 09/24/1999
• Status: Abandoned Application

• Current Assignee: Barnes-Jewish Hospital (BJC Health System)
• Original Assignee: Barnes-Jewish Hospital (BJC Health System)
• Inventors: Lanza, Gregory, Wickline, Samuel A.
• Application Number:
  US10/544,857
• Publication Number:
  US 20080247943A1
• Time in Patent Office: Days
• US Class Current: 424/1.37
• CPC Class Codes: A61K 47/6843 the antibody targeting a material from animals or humans
• CPC Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61K 49/1806 Suspensions, emulsions, colloids, dispersions
• CPC Class Codes: A61K 49/222 characterised by a special physical form, e.g. emulsions, liposomes
• CPC Class Codes: A61K 51/1018 against material from animals or humans
• CPC Class Codes: A61K 51/1227 Micelles, e.g. phospholipidic or polymeric micelles
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Emulsions comprising nanoparticles formed from high boiling perfluorochemical substances, said particles coated with a lipid/surfactant coating are made target-specific by directly coupling said nanoparticles to a targeting ligand. The nanoparticle may further include biologically active agents, radionuclides, and/or other imaging agents, and are used to image and/or lyse blood clots in human subjects.

Claims

1. A method to image and/or treat blood clots in human subjects, which method comprises administering to a subject in need of such diagnosis and/or treatment an emulsion of liquid, high-boiling perfluorocarbon-based nanoparticles, wherein said nanoparticles further comprise a coating of lipid/surfactant and which nanoparticles are coupled directly to at least one targeting ligand that is specific for at least one component characterizing blood clots, and

effecting said imaging or treatment.

2. The method of claim 1, which comprises administering said composition to said human subject systemically.

3. The method of claim 2, wherein said systemic administering is by intravenous administration.

4. The method of claim 1, wherein said method comprises administering said composition locally to said clot.

5. The method of claim 1, which method comprises obtaining an image of said clot using ultrasound, MRI or a radionuclide.

6. The method of claim 1, which method comprises effecting lysis or constrained propagation of said clot.

7. The method of claim 1, wherein said targeting ligand is coupled covalently to a component of the lipid/surfactant coating.

8. The method of claim 1, wherein said ligand binds specifically to fibrin.

9. The method of claim 1, wherein said nanoparticles further include at least one magnetic resonance imaging (MRI) contrast agent.

10. The method of claim 9, wherein said MRI contrast agent is a chelated paramagnetic ion.

11. The method of claim 10, wherein said chelating agent is DOTA and the paramagnetic ion is gadolinium ion.

12. The method of claim 1, wherein said nanoparticles further contain at least one radionuclide.

13. The method of claim 12, wherein said radionuclide is ⁹⁹Tc.

14. The method of claim 1, wherein said emulsion further includes at least one biologically active agent.

15. The method of claim 14, wherein said biologically active agent is a thrombolytic agent.

16. The method of claim 1, wherein said targeting ligand is an antibody, a fragment of an antibody, a peptide, an aptamer, a peptidomimetic or a receptor ligand.

17. The method of claim 16, wherein the targeting ligand is an antibody or fragment of an antibody.

18. The method of claim 17, wherein said antibody or fragment is humanized.