Uniform field magnetization and targeting of therapeutic formulations

• US 9,095,610 B2
• Filed: 09/30/2013
• Issued: 08/04/2015
• Est. Priority Date: 02/20/2004
• Status: Expired due to Fees

• Current Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation), Drexel University
• Original Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation), Drexel University
• Inventors: Levy, Robert J., Polyak, Boris, Chorny, Michael, Fishbein, Ilia, Alferiev, Ivan, Friedman, Gennady, Williams, Darryl
• Primary Examiner(s): Matthews, Christine H
• Assistant Examiner(s): LANNU, JOSHUA DARYL DEANON
• Application Number:
  US14/041,646
• Publication Number:
  US 20140170201A1
• Time in Patent Office: 673 Days
• Field of Search: 600 9- 15, 128897-899, 424/426, 424/93.6, 424/93.7, 514/44.A, 514/44.R, 514/449, 514/559
• US Class Current: 1/1
• CPC Class Codes: A61K 31/203 Retinoic acids ; Salts thereof
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61K 35/761 Adenovirus
• CPC Class Codes: A61K 41/00 Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/6455 Polycationic oligopeptides, polypeptides or polyamino acids, e.g. for complexing nucleic acids
• 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 47/6929 the form being a nanoparticle, e.g. an immuno-nanoparticle
• CPC Class Codes: A61K 48/0008 characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
• CPC Class Codes: A61K 48/0041 the non-active part being polymeric
• CPC Class Codes: A61K 48/0083 characterised by an aspect of the administration regime
• 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: A61K 9/5153 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/5169 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/5192 : Processes
• CPC Class Codes: C12N 15/111 : General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/86 : Viral vectors
• CPC Class Codes: C12N 2320/32 : Special delivery means, e.g. tissue-specific
• CPC Class Codes: C12N 2710/10343 : viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/10345 : Special targeting system for viral vectors

Abstract

Systems and methods for magnetic targeting of therapeutic particles are provided. Therapeutic particles comprise one or more magnetic or magnetizable materials and at least one therapeutic agent. Therapeutic particles are specifically targeted using uniform magnetic fields capable of magnetizing magnetizable materials, and can be targeted to particular locations in the body, or can be targeted for capture, containment, and removal. Also provided are bioresorbable nanoparticles prepared without the use of organic solvents, and methods for therapeutically using such bioresorbable nanoparticles.

Claims

1. A method for magnetically targeting a therapeutic particle to an intracorporeal device in a subject, comprising the steps of:

(a) administering to the subject at least one therapeutic particle comprising at least one therapeutic agent and a first magnetic or magnetizable material, wherein the at least one therapeutic particle is a microparticle or nanoparticle; and

(b) generating across the intracorporeal device a uniform magnetic field capable of magnetizing magnetizable materials, wherein the uniform magnetic field is provided by a magnetic field generator comprising first and second magnets and wherein the uniform magnetic field generates a magnetic field gradient proximal to the intracorporeal device, said intracorporeal device comprising a second magnetic or magnetizable material, wherein the gradient targets the at least one therapeutic particle to the intracorporeal device; and

(c) targeting the at least one therapeutic particle to the intracorporeal device via the magnetic field gradient;

wherein the step of generating the magnetic field comprises selectively placing the first and second magnets around the subject to direct the uniform magnetic field through the intracorporeal device.

2. The method of claim 1, wherein the at least one therapeutic agent comprises a pharmaceutical, biomolecule, or cell.

3. The method of claim 2, wherein the at least one therapeutic agent comprises a nucleic acid.

4. The method of claim 3, wherein the nucleic acid is a regulatory nucleic acid.

5. The method of claim 4, wherein the regulatory nucleic acid is siRNA, shRNA, or miRNA.

6. The method of claim 2, wherein the at least one therapeutic agent comprises an endothelial cell.

7. The method of claim 6, wherein the endothelial cell is a vascular endothelium cell.

8. The method of claim 1, wherein the intracorporeal device is a stent.

9. The method of claim 1, wherein the at least one therapeutic agent comprises an adenovirus.

10. The method of claim 1, wherein the step of administering at least one therapeutic particle to the subject comprises administering a plurality of therapeutic particles.

11. The method of claim 1, wherein the intracorporeal device is located in a peripheral artery of the subject.

12. The method of claim 1, wherein the intracorporeal device comprises grade 304 stainless steel.

13. The method of claim 1, wherein the step of generating a uniform magnetic field is performed after the step of administering the at least one therapeutic particle to the subject.

14. The method of claim 1, wherein the at least one therapeutic agent comprises paclitaxel.

15. The method of claim 1, further comprising a step of repeating steps (a), (b) and (c) to deliver an additional quantity of the at least one therapeutic agent to the intracorporeal device.