Therapeutic delivery using compounds self-assembled into high axial ratio microstructures

• US 5,851,536 A
• Filed: 11/21/1996
• Issued: 12/22/1998
• Est. Priority Date: 11/22/1995
• Status: Expired due to Fees

• Current Assignee: Washington University In St Louis
• Original Assignee: University of Washington
• Inventors: Carlson, Paul A., Lee, Kyujin C., Yager, Paul, Gelb, Michael H., Lukyanov, Anatoly N., Goldstein, Alex S.
• Primary Examiner(s): Kishore, Gollamudi S.
• Application Number:
  US08/752,848
• Time in Patent Office: 761 Days
• Field of Search: 424/400, 424/450, 424/443, 428/357, 428/221
• US Class Current: 424/400
• CPC Class Codes: A61K 47/6919 the form being a ribbon or a tubule cochleate
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Therapeutic agents comprising plural therapeutic compounds self assembled into high axial ratio microstructures are described. The threapeutic compounds satisfy the formula HARFM-Th, wherein HARFM is a high axial ratio forming material and Th is a therapeutic associated with the HARFM. The therapeutic agent also can satisfy the formula HARFM-S-Th, wherein S is a spacer. Release of the therapeutic by the agent generally follows either 0-order kinetics or psuedofirst order kinetics. A method for delivering drugs to animals or persons also is described. The method comprises administering an effective amount of a therapeutic self-assembled into an HAR microstructure to the animal or person.

Claims

1. A therapeutic agent comprising a covalent covalent complex according to the formula HARFM-Th, where HARFM is a high axial ratio forming microstructure material selected from the group consisting of tubules, cochleate cylinders, helical ribbons, twisted ribbons, and mixtures thereof the Th being a therapeutic covalently attached to molecules assembled into the high axial ratio microstructure.

2. The therapeutic agent according to claim 1 where the Th is attached to the HARM by a spacer.

3. The therapeutic agent according to claim 2 wherein the spacer is a polypeptide.

4. The therapeutic agent according to claim 3 wherein the polypeptide comprises an enzyme recognition site whereby enzymes can cleave the spacer at the recognition site.

5. The therapeutic agent according to claim 1 wherein the release of therapeutic by the agent follows 0-order kinetics.

6. A method for delivering the covalent complex of claim 1 to an animal or person, comprising administering an effective amount of the covalent complex self-assembled into a high axial ratio microstructure .

7. The therapeutic agent according to claim 1 wherein the therapeutic is a lipid.

8. The therapeutic agent according to claim 1 wherein the high axial ratio forming microstructure material is itself a therapeutic.

9. The therapeutic agent according to claim 1 wherein the therapeutic is selected from the group consisting of nucleic acids, conventional pharmaceuticals and mixtures thereof.

10. A therapeutic agent according to claim 9 wherein the nucleic acid is DNA.