Methods for targeted drug delivery

• US 20030129136A1
• Filed: 11/22/2002
• Published: 07/10/2003
• Est. Priority Date: 06/08/1995
• Status: Active Grant

• Current Assignee: Barnes-Jewish Hospital (BJC Health System)
• Original Assignee: Barnes-Jewish Hospital (BJC Health System)
• Inventors: Lanza, Gregory M., Wickline, Samuel A.
• Granted Patent: US 7,186,399 B2
• Time in Patent Office: Days
• US Class Current: 424/9.51
• 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 for enhancing the acoustic reflectivity of a surface in vivo comprising administering to said surface:

(a) a site-specific ligand; and

(b) a liquid emulsion having an outer coating composed of a material selected from the group consisting of a natural or synthetic phospholipid, a fatty acid, cholesterol, lipolipid, sphingomyelin, tocopherol, glucolipid, stearylamine, cardiolipin, a lipid with ether or ether linked fatty acids and a polymerized lipid;

said ligand being conjugated to said emulsion;

whereby the resulting ligand-emulsion conjugate is bound to said surface thereby causing enhancement of the acoustic reflectivity thereof for ultrasonic imaging or ultrasonic diagnostic applications.

2. A method as set forth in claim 1 wherein said ligand is conjugated to said emulsion through an intervening chemical group.

3. A method as set forth in claim 2 wherein said intervening chemical group is constituted by a hydrocarbon spacer.

4. A method as set forth in claim 1 wherein said method is carried out in vivo on a biological surface in a mammal.

5. A method as set forth in claim 1 wherein said emulsion contains a fluorocarbon.

6. A method as set forth in claim 1 wherein said ligand is selected from the group consisting of antibodies, viruses, chemotherapeutic agents, receptor agonists and antagonists, antibody fragments, lectins, albumins, peptides, hormones, amino sugars, lipids, fatty acids, nucleic acids, and cells prepared or isolated from natural or synthetic sources.

7. A method as set forth in claim 6 wherein said ligand is a monoclonal antibody.

8. A composition formed in vivo and enhancing the acoustic reflectivity of a surface to which it is bound, said composition comprising:

(a) a site-specific ligand; and

(b) a liquid emulsion having an outer coating composed of a material selected from the group consisting of a natural or synthetic phospholipid, a fatty acid, cholesterol, lipolipid, sphingomyelin, tocopherol, glucolipid, stearylarnine, cardiolipin, a lipid with ether or ether linked fatty acids and a polymerized lipid;

said ligand being conjugated to said emulsion with the resulting conjugate being bound to said surface thereby causing enhancement of the acoustic reflectivity thereof for ultrasonic imaging or ultrasonic diagnostic applications.

9. A composition as set forth in claim 8 wherein said ligand is conjugated to said emulsion through an intervening chemical group.

10. A composition as set forth in claim 9 wherein said intervening chemical group is constituted by a hydrocarbon spacer.