Functionalized Magnetic Nanoparticles and Methods of Use Thereof

• US 20080206146A1
• Filed: 03/21/2006
• Published: 08/28/2008
• Est. Priority Date: 03/21/2005
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Engel, Jerome, Akhtari, Massoud
• Application Number:
  US11/817,949
• Publication Number:
  US 20080206146A1
• Time in Patent Office: Days
• US Class Current: 424/9.3
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 47/62 the modifying agent being a protein, peptide or polyamino acid
• 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 49/1854 the organic macromolecular compound being obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly(meth)acrylate, polyacrylamide, polyvinylpyrrolidone, polyvinylalcohol
• CPC Class Codes: A61K 49/1863 the organic macromolecular compound being a polysaccharide or derivative thereof, e.g. chitosan, chitin, cellulose, pectin, starch
• CPC Class Codes: A61K 49/1869 coated or functionalised with a protein being an albumin, e.g. HSA, BSA, ovalbumin
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The present invention provides functionalized magnetic nanoparticles comprising a functional group, which functionalized magnetic nanoparticles exhibit differential binding to a tissue, indulging brain tissue, bone, and vascular tissues. The present invention further provides compositions, including pharmaceutical compostions, comprising a subject functionalized magnetic nanoparticle. The present invention further provides diagnostic and research methods including use of subject functionized magnetic nanoparticles. The present invention further provides a magnetic resonance imaging (MRI)-visible drug delivery system; drugs using MRI, as well as tissue-specific drug delivery.

Claims

1. A pharmaceutical composition comprising:

a) a functionalized magnetic nanoparticle (MNP) comprising a functional group that has differential affinity for a tissue in the brain, wherein said functionalized magnetic nanoparticle is capable, when introduced into the bloodstream of a mammalian subject, of crossing the blood-brain barrier of said subject and binding specifically to the brain tissue; and

b) a pharmaceutically acceptable carrier.

2. The composition of claim 1, wherein the tissue is a diseased tissue.

3. The composition of claim 2, wherein the diseased tissue is selected from a brain tumor, an epileptic lesion, a plaque associated with Alzheimer'"'"'s Disease, a tissue affected by multiple sclerosis, a tissue affected by Huntington'"'"'s Disease, a tissue affected by Parkinson'"'"'s Disease, and a tissue affected by amyotropic lateral sclerosis.

4. The composition of claim 1, wherein the tissue is one that is exposed to an external or internal stimulus.

5. The composition of claim 1, wherein said functional group is an antibody that specifically binds an epitope present in the brain tissue.

6. The composition of claim 1, wherein said functional group is a ligand that binds specifically to a receptor present on or in a cell present in the brain tissue.

7. The composition of claim 1, wherein the functionalized MNP further comprises a therapeutic agent.

8. The composition of claim 1, wherein the functionalized MNP is encapsulated in an albumin matrix.

9. The composition of claim 1, where the functionalized MNP comprises an apolipoprotein.

10. The composition of claim 1, wherein the functionalized MNP comprises poly(butyl cyanoacrylate) (PBCA).

11. The composition of claim 10, wherein the functionalized MNP is attached to the surface of a PBCA particle.

12. The composition of claim 1, wherein the functionalized MNP comprises a surfactant.

13. The composition of claim 12, wherein the surfactant is selected from polyoxyethylene sorbitan monooleate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monostearate, and polyoxyethylene sorbitan monolaurate.

14. The composition of claim 12, wherein the surfactant is a block copolymer of polyethylene oxide and polypropylene oxide.

15. The composition of claim 12, wherein the functionalized MNP comprises a poloxamine.

34. A method of treating a disorder in an individual, the method comprising:

administering to an individual in need thereof an effective amount of a composition of claim 1.

35. The method of claim 34, wherein the functionalized MNP further comprises a therapeutic agent that treats the disorder.

16. A pharmaceutical composition comprising:

a) a functionalized magnetic nanoparticle comprising a functional group that has differential affinity for an inflamed vascular tissue that is at risk of restenosis, wherein said functionalized magnetic nanoparticle is capable, when injected into the bloodstream of a mammalian subject, of binding specifically to the inflamed vascular tissue; and

b) a pharmaceutically acceptable carrier.

17. A pharmaceutical composition comprising:

a) a functionalized magnetic nanoparticle comprising a functional group that has differential affinity for a diseased bone tissue, and wherein said functionalized magnetic nanoparticle is capable, when injected into the bloodstream of a mammalian subject, of binding specifically to the diseased bone tissue; and

b) a pharmaceutically acceptable carrier.

18. The composition of claim 17, wherein the bone tissue is inflamed as a result of diabetes, injury, or other compromising factors causing an inflammatory response in the bone tissue.

19. A pharmaceutical composition comprising:

a) a magnetic nanoparticle that is derivatized with a functional group that has differential affinity for epileptic tissue in the brain, and wherein said magnetic nanoparticle is capable, when injected into the bloodstream of a mammalian subject, of crossing the blood-brain barrier of said subject and binding specifically to epileptic tissue in the brain; and

b) a pharmaceutically acceptable carrier.

20. The pharmaceutical composition of claim 19, wherein the functional group is glucose.

21. The pharmaceutical composition of claim 19, wherein the functional group is N-methyl-D-aspartate.

22. The pharmaceutical composition of claim 19, wherein the functional group is α

-methyl tryptophan.

23. The pharmaceutical composition of claim 19, wherein the functional group is a cytokine.

24. The pharmaceutical composition of claim 19, wherein the functional group is γ

-amino butyric acid.

25. The pharmaceutical composition of claim 19, wherein the functional group is an opiate or an opioid compound.

26. A method of diagnosing a brain disorder, the method comprising:

a) administering to a mammalian subject a composition comprising a functionalized magnetic nanoparticle, wherein said functionalized magnetic nanoparticle comprises a functional group that has differential affinity for a tissue in the brain that is affected by the brain disorder, and wherein said functionalized magnetic nanoparticle is capable, when injected into the bloodstream of the mammalian subject, of crossing the blood-brain barrier of said subject; and

b) detecting the presence of the functionalized magnetic nanoparticle in the brain.

27. The method of claim 26, wherein the brain disorder is selected from a brain tumor, epilepsy, Alzheimer'"'"'s Disease, multiple sclerosis, Huntington'"'"'s Disease, Parkinson'"'"'s Disease, amyotropic lateral sclerosis, a drug addition, and a psychiatric disorder.

28. The method of claim 26, wherein the composition is administered by intravenous injection.

29. The method of claim 26, wherein said detecting is by magnetic resonance imaging.

30. A method of detecting a vascular tissue that is at risk of restenosis, the method comprising:

a) administering to a mammalian subject a composition comprising a functionalized magnetic nanoparticle, wherein said functionalized magnetic nanoparticle comprises a functional group that has differential affinity for an inflamed vascular tissue, and wherein said functionalized magnetic nanoparticle is capable, when injected into the bloodstream of the mammalian subject, of binding specifically to the inflamed vascular tissue; and

b) detecting the presence of the functionalized magnetic nanoparticle in the vascular tissue.

31. A method of detecting a diseased bone tissue in a mammalian subject, the method comprising:

a) administering to a mammalian subject a composition comprising a functionalized magnetic nanoparticle, wherein said functionalized magnetic nanoparticle comprises a functional group that has differential affinity for diseased bone tissue, and wherein said functionalized magnetic nanoparticle is capable, when injected into the bloodstream of the mammalian subject, of binding specifically to the diseased bone tissue; and

b) detecting the presence of the functionalized magnetic nanoparticle in the bone tissue.

32. A method of identifying an agent that treats a brain disorder, the method comprising:

administering a test agent to a non-human animal model of a brain disorder; and

determining the effect, if any, of the test agent on a neurological feature of the brain disorder, wherein said determining is carried out by;

i) administering to the non-human animal model a composition comprising a functionalized magnetic nanoparticle, wherein the functionalized magnetic nanoparticle exhibits differential binding to a diseased brain tissue affected by or associated with the neurological disorder; and

ii) detecting the functionalized magnetic nanoparticle in the brain of the animal.

33. The method of claim 32, wherein said detecting is by magnetic resonance imaging.