Multi-arm cyclic or cubic siloxane-based formulations for drug delivery

• US 7,745,547 B1
• Filed: 08/07/2006
• Issued: 06/29/2010
• Est. Priority Date: 08/05/2005
• Status: Expired due to Fees

• Current Assignee: Becton, Dickinson & Co, City College of New York
• Original Assignee: Becton, Dickinson & Co, The Research Foundation of State University of New York
• Inventors: Chauhan, Bhanu P. S., Latif, Umar, Clarke, Richard P., Auerbach, Andrew, Haider, M. Ishaq
• Primary Examiner(s): Gulakowski; Randy
• Assistant Examiner(s): BLAND, ALICIA
• Application Number:
  US11/500,175
• Time in Patent Office: 1,422 Days
• Field of Search: 514/63, 514/740, 514/579, 424/450, 424/484, 424/486, 428/402.2, 556/434, 556/450, 556/462, 556/464, 556/465, 556/467, 528 10- 31, 528/33, 528/37, 525/409, 524/588
• US Class Current: 525/409
• CPC Class Codes: A61K 47/52 the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: C08G 65/336 containing silicon
• CPC Class Codes: C08L 2203/02 for biomedical use

Abstract

The present invention provides multi-arm siloxane-based molecules suitable for use as a drug delivery vehicle comprising a central core molecule that comprises a cyclic or cubic siloxane, and a plurality of arms attached to the central core molecule, wherein each arm comprises an organic moiety. The multi-arm siloxane-based molecules described herein are suitable for encapsulation of a therapeutic agent. The invention further includes pharmaceutical compositions comprising the claimed multi-arm siloxane-based molecules and an encapsulated therapeutic agent in combination with a pharmaceutically acceptable carrier. Methods of making and using the multi-arm siloxane-based molecules are also provided.

Claims

1. A multi-arm siloxane-based molecule for use as a drug delivery vehicle comprising a central core molecule that comprises a cyclic siloxane and a plurality of arms attached to the central core molecule, wherein each arm comprises an organic moiety, and wherein one or more of insulin, cisplatin, or paclitaxel is encapsulated in the molecule.

2. The multi-arm siloxane-based molecule of claim 1, wherein the central core molecule is tetramethylcyclotetrasiloxane or pentamethylcyclopentasiloxane.

3. The multi-arm siloxane-based molecule of claim 1, wherein the central core molecule is attached to about 3 to about 10 arms.

4. The multi-arm siloxane-based molecule of claim 3, wherein the central core molecule is attached to about 4 to about 8 arms.

5. The multi-arm siloxane-based molecule of claim 1, wherein the organic moiety of each arm comprises a polyethylene glycol (PEG).

6. The multi-arm siloxane-based molecule of claim 5, wherein the PEG has a molecular weight of about 400 Da to about 1500 Da.

7. The multi-arm siloxane-based molecule of claim 5, wherein the PEG has a molecular weight of about 400 Da.

8. The multi-arm siloxane-based molecule of claim 5, wherein the PEG has a molecular weight of about 1000 Da.

9. The multi-arm siloxane-based molecule of claim 5, wherein the PEG is selected from the group consisting of PEG-tetrahydrofurfuryl ether, PEG-methyl ether 350, and PEG-methyl ether 550.

10. The multi-arm siloxane-based molecule of claim 1, wherein the molecule is selected from the group consisting of (PEG400)₄D₄^M, (PEG1000)₄D₄^M, (PEG400)₅D₅^M, (PEG-THF ether)₄D₄^M, DA₄D₄^M, BE₄D₄^M, [PEGMetEt(350)]₄D₄^M, and [PEGMetEt(550)]₄D₄^M.

11. A composition comprising a plurality of the multi-arm siloxane-based molecule of claim 1.

12. The composition of claim 11, wherein the plurality of multi-arm siloxane based molecules form a micellar structure in a solution.

13. A pharmaceutical composition comprising the multi-arm siloxane-based molecule of claim 1 and a pharmaceutically acceptable carrier.

14. A pharmaceutical composition comprising:

a multi-arm siloxane-based molecule for use as a drug delivery vehicle comprising a central core molecule that comprises a cyclic siloxane and a plurality of arms attached to the central core molecule, wherein each arm comprises a PEG selected from the group consisting of PEG-tetrahydrofurfuryl ether, PEG-methyl ether 350, and PEG-methyl ether 550;

a therapeutic agent selected from the group consisting of anticancer agents, diabetes-controlling agents, antibiotics, antifungal agents, antiviral agents, anti-inflammatory drugs, migraine drugs, anti-anxiety agents, hormones, growth factors, steroidal agents, cardiovascular agents, and combinations thereof; and

a pharmaceutically acceptable carrier.

15. The multi-arm siloxane-based molecule of claim 14, wherein the central core molecule is tetramethylcyclotetrasiloxane or pentamethylcyclopentasiloxane.

16. The multi-arm siloxane-based molecule of claim 14, wherein the central core molecule is attached to about 3 to about 10 arms.

17. The multi-arm siloxane-based molecule of claim 14, wherein the central core molecule is attached to about 4 to about 8 arms.

18. A composition comprising a plurality of the multi-arm siloxane-based molecule of claim 14.

19. A pharmaceutical composition comprising the multi-arm siloxane-based molecule of claim 14 having at least one therapeutic went encapsulated within the molecule and a pharmaceutically acceptable carrier.

20. A pharmaceutical composition comprising

a plurality of siloxane-based molecules for use as a drug delivery vehicle comprising a central core molecule that comprises a cyclic siloxane and a plurality of arms attached to the central core molecule, wherein each arm comprises an organic moiety, wherein the plurality of multi-arm siloxane based molecules forms a micellar structure in a solution;

a therapeutic agent selected from the group consisting of anticancer agents, diabetes-controlling agents, antibiotics, antifungal agents, antiviral agents, anti-inflammatory drugs, migraine drugs, anti-anxiety agents, hormones, steroidal agents, cardiovascular agents, and combinations thereof; and

a pharmaceutically acceptable carrier.