On-demand drug release using magneto-electric nanoparticles

• US 9,724,503 B2
• Filed: 05/04/2015
• Issued: 08/08/2017
• 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: Ping Liang, The Florida International University Board of Trustees (State University System of Florida)
• Inventors: Khizroev, Sakhrat, Guduru, Rakesh, Liang, Ping
• Primary Examiner(s): Azpuru, Carlos
• Application Number:
  US14/703,521
• Publication Number:
  US 20160030724A1
• Time in Patent Office: 827 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 47/6851 the antibody targeting a determinant of a tumour cell
• CPC Class Codes: A61K 47/6871 the antibody targeting an enzyme
• CPC Class Codes: A61K 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61K 47/6943 the form being a pill, a tablet, a lozenge or a capsule
• 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 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• 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: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61N 1/327 for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 2/002 in combination with another treatment
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B82Y 25/00 : Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
• 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 of treating a subject, comprising:

administering to the subject a plurality of magneto-electric nanoparticles (MENP) having a drug associated thereto; and

applying a magnetic field to the subject to generate electric fields on membranes of cells to which the plurality of MENP are adjacent such that the magnetic field strength is sufficient to generate an electric field capable of causing nano-electroporation sites to develop on targeted disease cells but not strong enough to cause nano-electroporation sites on other cells.

2. The method of claim 1, wherein the strength of the magnetic field is increased after nano-electroporation sites are formed on the targeted disease cells in order to release the drug from the plurality of MENP.

3. The method of claim 1, wherein each of the plurality of MENP further comprise a biomarker-specific antibody.

4. The method of claim 1, wherein the drug is an anti-neoplastic drug.

5. The method of claim 1, wherein the disease cells comprise cancer cells.

6. The method of claim 2, wherein the strength of the magnetic field to cause nano-electroporation sites to develop on targeted disease cells, has a value denoted by H_th, and the strength of the magnetic field in order to release the drug from the MENP, has a value denoted by Hr, and Hr>

H_th, wherein H_th is determined by electric properties of cell membrane of the targeted disease cells that lead to localized electroporation effects.

7. The method of claim 6, further comprising adding intermediate layers or coatings between the drug and the MENP to control the Hr.

8. The method of claim 7, wherein Hr has a value between 10 Oe to 200 Oe.

9. The method of claim 1, wherein the magnetic field directs the plurality of MENP adjacent to the targeted disease cells.

10. A method as defined in claim 1, wherein the magnetic field comprises a direct current (DC) field.

11. A method as defined in claim 1, wherein the plurality of MENP comprise CoFe₂O₄@BaTiO₃.

12. A method for treating diseased cells in a human subject, comprising:

administering to the subject a plurality of magneto-electric nanoparticles (MENP) having a drug associated thereto;

applying a magnetic field to the subject to generate electric fields on membranes of cells to which the plurality of MENP are adjacent whereas the strength of the magnetic field is such that it generates an electric field strong enough to cause nano-electroporation sites to develop on the targeted disease cells but not strong enough to cause nano-electroporation sites on other cells; and

applying a magnetic field equal to or greater than a release field threshold after nano-electroporation sites have developed in order to release the drug from the plurality of MENPs.

13. A method as defined in claim 12, wherein the magnetic field used to develop the nano-electroporation sites on the targeted disease cells comprises a direct current (DC) field.

14. A method as defined in claim 13, wherein the magnetic field used to release the drug from the MENP comprises an alternating current (AC) field.

15. A method as defined in claim 12, wherein the magnetic field used to release the drug from the MENP comprises an alternating field.

16. A method as defined in claim 12, where the magnetic field used to release the drug from the MENP is stronger than the magnetic field for nano-electroporation.