Magnetic nanoparticle compositions, and methods related thereto

Magnetic nanoparticle compositions, and methods related thereto

Agent: Pepper Hamilton LLP One Mellon Center - Pittsburgh, PA, US
Inventors: Cordula Gruettner, Joachim Teller, Fritz Westphal, Robert Ivkov
Class: 424646000 (USPTO)
#20050271745
12/08/05
Disclosed are biocompatible magnetic nanoparticle compositions for various therapeutic or biological applications, and methods related thereto. Specifically, the present invention pertains to magnetic nanoparticle compositions prepared via high-pressure homogenization processes that include a turbulent flow zone. The methods of production may involve a two-step or a one-step process. The disclosed magnetic nanoparticle compositions may be useful in the treatment of the body, body part, tissue, cell, or body fluid of a subject for a variety of indications. The disclosed magnetic nanoparticle compositions may also be useful in the fixation, separation, transportation, marking or coding of targets, or energy transformation processes.
TECHNICAL FIELD
[0002] The present invention relates generally to biocompatible magnetic nanoparticle compositions for various biological and therapeutic applications, and methods related thereto. Specifically, the present invention pertains to magnetic nanoparticle compositions prepared via high-pressure homogenization processes that include a turbulent flow zone.
SUMMARY OF THE INVENTION
[0009] Various methods for producing magnetic nanoparticle compositions exist. However, a major problem has been the inability to produce biocompatible magnetic nanoparticle compositions having enhanced homogeneity, especially those having high metallic content and high magnetic mobility.
[0010] In view of the above, there is a need for biocompatible magnetic nanoparticle compositions that have enhanced homogeneity and comprise high metallic content nanoparticles possessing high magnetic mobility. There is also a need for methods for producing such compositions.
[0011] It is, therefore, an aspect of the present invention to provide biocompatible magnetic nanoparticle compositions having enhanced homogeneity.
[0012] It is also an aspect of the present invention to provide magnetic nanoparticle compositions comprising high metallic content nanoparticles that possess high magnetic mobility.
[0013] It is another aspect of the present invention to provide methods for producing magnetic nanoparticle compositions, particularly with the use of high-pressure homogenization processes that include a turbulent flow zone.
[0014] It is another aspect of the present invention to provide applications for biocompatible magnetic nanoparticle compositions comprising high metallic content nanoparticles that possess high magnetic mobility.
[0015] The present invention pertains to biocompatible magnetic nanoparticle compositions that possess high metallic content and exhibit enhanced homogeneity and high magnetic mobility, which contributes to higher heating rates. Higher heating rates are desirable for various therapeutic applications. These compositions are preferably prepared via high-pressure homogenization processes, and are useful for various therapeutic and biological applications.
[0016] In one embodiment, the magnetic nanoparticle composition comprises one or more metal-containing magnetic nanoparticles and a suitable medium for suspending the nanoparticles. The nanoparticles comprise a suitable biocompatible coating material. The magnetic nanoparticles possess a low-field magnetization when an external magnetic field is applied to the magnetic nanoparticles. The magnetic material of the nanoparticles exhibits a low-field magnetization greater than that of the material from which it was derived. The nanoparticles have at least an average 50 mass percent of metal and an average hydrodynamic diameter of less than 200 nm.
[0017] In another embodiment, the magnetic nanoparticle composition is prepared via a two-step process wherein a preformed metal-containing magnetic material is processed through a turbulent flow zone in a first step, and the resulting improved magnetic material of the first step is utilized in combination with a biocompatible coating material to generate a magnetic nanoparticle composition, via a turbulent flow zone in a second step. In another embodiment, the magnetic nanoparticle composition is prepared via a two-step process wherein a metal-containing magnetic material is generated from a metal-containing solution, via a turbulent flow zone, in a first step, and the resulting magnetic material of the first step is utilized in combination with a biocompatible coating material to generate a magnetic nanoparticle composition, via a turbulent flow zone, in a second step. In another embodiment, the magnetic nanoparticle composition is prepared via a one-step process wherein a metal-containing magnetic material is generated from a metal-containing solution, and processed with a biocompatible coating material, via a turbulent flow zone, to form a magnetic nanoparticle composition. The resulting magnetic nanoparticles may be separated from the carrier medium by an external magnetic field, for example, via permanent magnets.
[0018] The biocompatible coating material may comprise a polymer, metal compound, transfection agent, or any combination thereof. The polymer may comprise a naturally occurring, synthetic, or semi-synthetic polymer. Preferably, the polymer is dextran or dextran that contains functional groups, e.g., sulfoalkyl, aminoalkyl, epoxyalkyl and carboxyalkyl whereby the alkyl chain may be substituted with heteroatoms, e.g., oxygen. The metal-containing magnetic material comprises a metal, metal oxide, metal oxide-hydrate, metal hydroxide, metallic alloy of two or more metals, or any combination thereof. The metal-containing magnetic material has ferro-, antiferro-, ferri-, antiferri- or superparamagnetic properties. Preferably, the metal-containing magnetic material comprises an oxide of iron, more preferably, the iron oxide is magnetite, hematite, maghemite, or any combination thereof. The magnetic nanoparticle composition may also comprise sub-structures that may comprise ligands or chelators, or that may comprise one or more bioactive substances.
[0019] The present invention also pertains to applications for biocompatible magnetic nanoparticle compositions, namely therapeutic and biological applications. The therapeutic applications pertain to the treatment of the body, body part, tissue, cell, or body fluid of a subject for a variety of indications, including but not limited to, cancer of any type, such as bone marrow, lung, vascular, neuro, colon, ovarian, breast and prostate cancer, epitheleoid sarcomas, adverse angiogenesis, restenosis, amyloidosis, tuberculosis, multiple sclerosis, cardiovascular plaque, vascular plaque, obesity, malaria, and illnesses due to viruses, such as HIV and AIDS. The therapeutic compositions may be administered via injection, topical application, transdermal application, oral ingestion, rectal insertion, inhalation through the mouth or nose, or any combination thereof. The biological applications include fixation, separation, transportation, marking or coding of targets, or energy transformation processes. The magnetic nanoparticle compositions may also be used in the separation, purification, or any combination thereof of nucleic acids, nucleic acid derivatives, nucleic acid fragments, proteins, protein derivatives, protein fragments, or any combination thereof.
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