ON-DEMAND DRUG RELEASE USING MAGNETO- ELECTRIC NANOPARTICLES

• US 20150283368A1
• Filed: 11/06/2013
• Published: 10/08/2015
• Est. Priority Date: 11/06/2012
• Status: Active Grant

• Current Assignee: The Florida International University Board of Trustees (State University System of Florida)
• Original Assignee: The Florida International University Board of Trustees (State University System of Florida)
• Inventors: Khizroev, Sakhrat, Nair, Madhavan P.N., Liang, Ping, Runowicz, Carolyn, Guduru, Rakesh
• Granted Patent: US 9,895,549 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 41/0028 Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
• CPC Class Codes: A61K 47/6923 the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/5094 Microcapsules containing magnetic carrier material, e.g. ferrite for drug targeting
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5146 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
• CPC Class Codes: A61N 2/00 Magnetotherapy
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Disclosed herein are methods of delivering drugs to a subject in a controlled release fashion by administering a magneto-electric nanoparticle having ionic bonds to a drug then applying a magnetic field to weaken the ionic bonds and release the drug.

Claims

1. A method comprising

administering to a subject a plurality of magneto-electric nanoparticles (MENP) having (i) a coating on at least a portion of the MENP surface, said coating one or more of glycerol monooleate, poly L-lysine and polyethylene glycol, and (ii) a drug associated with the MENP through an ionic bond;

and

applying a magnetic field to the subject to weaken the ionic bond thereby releasing at least a portion of the drug from the MENP.

2. The method of claim 1, wherein the MENP comprises CoFe₂O₄ @ BaTiO₃.

7. The method of claim 1, wherein the magnetic field has a strength of at least 10 Oe.

12. The method of claim 1, wherein the magnetic field has a frequency of about 10 Hz to about 100 Hz or about 500 Hz to about 1000 Hz.

15. The method of claim 1, wherein the drug is a HIV drug.

16. The method of claim 15, wherein the drug is AZTTP.

17. The method of claim 1, wherein the drug is an anticancer drug.

18. The method of claim 17, wherein the drug comprises paclitaxel.

19. The method of claim 1, wherein the MENP further comprises a chemical tagging agent.

20. The method of claim 19, wherein the chemical tagging agent is a cancer antigen.

24. The method of claim 1, wherein the coating layer comprises glycerol monooleate.

25. The method of claim 1, wherein the applying step is for a specific time and at a specific magnetic field strength so as to release a predetermined amount of drug.

29. The method of claim 1, wherein the amount of drug released after application of the magnetic field is at least 20% of the total amount bound to the MENP.

30. The method of claim 1, further comprising repeating the applying of the magnetic field a second time to release a second portion of the drug from the MENP.

31. The method of claim 30, wherein the second applying step is separated from the first applying step by at least 1 hour.

34. The method of claim 1, wherein at least 95% of the drug is released from the MENP after administration to the subject.

3-6. -6. (canceled)

8-11. -11. (canceled)

13-14. -14. (canceled)

21-23. -23. (canceled)

26-28. -28. (canceled)

32-33. -33. (canceled)

35. (canceled)

36. A method comprising

administering to a subject a plurality of magneto-electric nanoparticles (MENP) having a coating layer and a drug associated with at least a portion of the surface of the MENP through an ionic bond;

and

applying a magnetic field to the subject to weaken the ionic bond thereby releasing at least a portion of the drug from the MENP, wherein the coating layer comprises one or more of glycerol monooleate, polyethylene glycol, and poly-L-lysine, and the MENP comprises CoFe₂O₄@BaTiO₃.

37. A method of treating cancer in a subject suffering therefrom comprising:

administering to the subject a composition comprising a plurality of magneto-electric nanoparticles (MENP) having (i) a coating layer comprising glycerol monooleate and (ii) an anticancer drug associated with the coating layer, the MENP, or both, through an ionic bond; and

applying a magnetic field to the subject to weaken the ionic bond thereby releasing at least a portion of the drug from the MENP.

38. The method of claim 37, wherein the cancer is ovarian cancer and the anticancer drug comprises paclitaxel.

39. The method of claim 37, wherein the MENP further comprises a cancer antigen.