Methods for targeted drug delivery

• US 7,186,399 B2
• Filed: 11/22/2002
• Issued: 03/06/2007
• Est. Priority Date: 06/08/1995
• Status: Expired due to Fees

• Current Assignee: Barnes-Jewish Hospital (BJC Health System)
• Original Assignee: Barnes-Jewish Hospital (BJC Health System)
• Inventors: Lanza, Gregory M., Wickline, Samuel A.
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US10/302,369
• Publication Number:
  US 20030129136A1
• Time in Patent Office: 1,565 Days
• Field of Search: 424/489, 424/455, 424/9.5, 424/9.51, 424/9.52, 424/9.3, 424/9.32, 514/937, 514/938
• US Class Current: 424/9.3
• CPC Class Codes: A61K 49/18 characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
• CPC Class Codes: A61K 49/1812 liposomes, polymersomes, e.g. immunoliposomes
• CPC Class Codes: A61K 51/1217 Dispersions, suspensions, colloids, emulsions, e.g. perfluorinated emulsion, sols
• CPC Class Codes: G01N 33/586 Liposomes, microcapsules or cells

Abstract

A method for ligand-based binding of lipid encapsulated particles to molecular epitopes on a surface in vivo or in vitro comprises sequentially administering (a) a site specific ligand activated with a biotin activating agent; (b) an avidin activating agent; and (c) lipid encapsulated particles activated with a biotin activating agent, whereby the ligand is conjugated to the particles through an avidin-biotin interaction and the resulting conjugate is bound to the molecular epitopes on such surface. The conjugate is effective for imaging by x-ray, ultrasound, magnetic resonance or positron emission tomography. Compositions for use in ultrasonic imaging of natural or synthetic surfaces and for enhancing the acoustic reflectivity thereof are also disclosed.

Claims

1. A method to effect delivery of a therapeutic agent into a target tissue of a subject in vivo which method comprises

(a) administering to said subject an emulsion of particles that consist of lipid-coated liquid perfluorocarbon and at least one therapeutic agent which particles are directly coupled to a ligand specific for said target tissue, and

(b) delivering said therapeutic agent to said target tissue while said particles are entirely in the liquid state.

2. The method of claim 1 wherein said ligand comprises an antibody or fragment thereof, a virus, a receptor agonist or antagonist, a hormone, or a nucleic acid.

3. The method of claim 2 wherein the ligand comprises an antibody or fragment thereof or a receptor agonist or antagonist.

4. The method of claim 3 wherein the ligand is an antibody or fragment thereof.

5. The method of claim 1 wherein the therapeutic agent is a drug or a radioactive agent.

6. The method of claim 5 wherein the drug is tissue plasminogen activator, adriamycin, vincristine, urokinase, streptokinase, methotrexate, cytarabine, thioguanine, 5-fluorouracil, cisplatin, etoposide, ifosfamide, asparaginase, deoxycoformycin or hexamethyl melamine.

7. The method of claim 1 which further comprises obtaining an ultrasonic image or magnetic resonance image of said target tissue.

8. The method of claim 1 wherein said target tissue is a thrombus or cancer.

15. The method of claim 1 wherein said perfluorocarbon consists of perfluorotributylamine, perfluorodecalin, perfluorooctylbromide, perfluorodichlorooctane, perfluorodecane, perfluorotripropylamine, perfluorotrimethylcyclohexane, or mixtures of the foregoing.

9. An emulsion which comprises particles consisting of liquid perfluorocarbon coated with lipid and at least one therapeutic agent, wherein said particles are directly coupled to a ligand specific for a target tissue, wherein said perfluorocarbon consists of perfluorotributylamine, perfluorodecalin, perfluorooctylbromide, perfluorodichlorooctane, perfluorodecane, perfluorotripropylamine, perfluorotrimethylcyclohexane, or mixtures of the foregoing.

10. The emulsion of claim 9 wherein said ligand comprises an antibody or fragment thereof, a virus, a receptor agonist or antagonist, a hormone, or a nucleic acid.

11. The emulsion of claim 10 wherein the ligand comprises an antibody or fragment thereof or a receptor agonist or antagonist.

12. The emulsion of claim 11 wherein the ligand is an antibody or fragment thereof.

13. The emulsion of claim 9 wherein the therapeutic agent is a drug or a radioactive agent.

14. The emulsion of claim 13 wherein the drug is tissue plasminogen activator, adriamycin, vincristine, urokinase, streptokinase, methotrexate, cytarabine, thioguanine, 5-fluorouracil, cisplatin, etoposide, ifosfamide, asparaginase, deoxycoformycin or hexamethyl melamine.