Magnetic microparticles comprising organic substances

• US 20070281034A1
• Filed: 05/15/2007
• Published: 12/06/2007
• Est. Priority Date: 05/15/2006
• Status: Abandoned Application

• Current Assignee: Daniel Chan, Dmitri Kirpotin, Paul Bunn
• Original Assignee: Daniel Chan, Dmitri Kirpotin, Paul Bunn
• Inventors: Bunn, Paul, Chan, Daniel, Kirpotin, Dmitri
• Application Number:
  US11/803,902
• Publication Number:
  US 20070281034A1
• Time in Patent Office: Days
• US Class Current: 424/489
• CPC Class Codes: A61K 47/6935 the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
• CPC Class Codes: A61K 47/6939 the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
• CPC Class Codes: A61K 49/1857 the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
• 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: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 241/46 Phenazines
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 493/08 Bridged systems

Abstract

The invention provides for water-dispersible microparticles comprising magnetic material and organic substance, such as a pharmaceutical or a pigment, that constitute in totality at least 50%, or preferably more that 70%, of the dry mass of the particle. The method of making such microparticles is also provided, comprising coating of the magnetic material in an aqueous colloid form with a layer of a polyelectrolyte, and combining the coated colloid with the organic substance having ionic charge opposite to that of the polyelectrolyte. When the organic substance is poorly soluble in water, the combining comprises dissolving of the substance in a water-miscible organic solvent, and combining said solution with the polyelectrolyte-coated magnetic colloid. The magnetic pharmaceutical microparticles are useful for magnetically-guided drug delivery, and/or for non-invasive monitoring of the drug distribution in the body. Magnetic microparticles comprising dyes and pigments are useful in magnetic inks.

Claims

1. A composition comprising microparticles, said microparticles comprising:

(i) a magnetic substance;

(ii) a polymer associated with said magnetic substance, said polymer having functional groups ionizable to produce a charge sign; and

(iii) an ionizable organic compound,

wherein said ionizable organic compound in aqueous medium is ionizable to the charge sign opposite to that of said polymer, and

wherein said magnetic substance and said organic compound in totality constitute at least 50% of the microparticle dry mass, and

wherein said microparticles are dispersible in water.

2. A composition of claim 1 wherein said magnetic substance and said organic compound in totality constitute at least 70% of the microparticle dry mass, or at least 90% of the microparticle dry mass.

3. A composition of claim 2 wherein said organic compound constitutes at least 10% of the microparticle dry mass.

4. A composition of claim 1 wherein said organic compound is poorly soluble in water.

5. A composition of claim 1 wherein said organic compound is a pharmaceutical, a dye, or a pigment.

6. A composition of claim 5 wherein said organic compound is an anticancer drug, an antimicrobial drug, doxorubicin, methotrexate, dexniguldipine, clofazimine, or amphotericin B.

7. A composition of claim 1 wherein said magnetic substance is ferrite, magnetite, or maghemite.

8. A composition of claim 5 wherein said organic substance is a pharmaceutical, and said microparticle comprises on its surface a coating effective to extend the microparticle blood circulation time.

9. A composition of claim 1 wherein said microparticle comprises on its surface a coating comprising a hydrophilic polymer, a poly(alkyl ether), or poly(ethylene glycol).

10. A composition of claim 5 wherein said microparticle comprises a targeting moiety.

11. A composition of claim 9 wherein said microparticle comprises a targeting moiety linked to said coating.

12. A composition of claim 1 wherein said organic substance is a pharmaceutical, and microparticles are in a pharmaceutically acceptable medium.

13. A composition of claim 1 wherein said microparticles have the average size between about 10 nanometers and about 10 micrometers, or between about 30 nanometers and about 3 micrometers.

14. A composition of claim 1 wherein said magnetic substance in the form of a ferromagnetic, paramagnetic, or superparamagnetic nanoparticle, said nanoparticle having at least one magnetic domain.

15. A composition of claim 14 wherein said nanoparticle of said magnetic substance has the size between about 1 nm and about 100 nm.

27. A method of treatment of a patient comprising administering to the patient an effective amount of the composition of claim 12.

16. A method of making a microparticle-containing composition, said method comprising the step of contacting a magnetic substance dispersed in a liquid medium and having a charged polymer associated with said magnetic substance and ionized in said medium to attain a charge sign, with an ionizable organic compound attaining in said medium a charge sign opposite to that of said charged polymer, to effect formation of a microparticle.

17. A method of claim 16 wherein magnetic substance and said organic compound in totality constitute at least 50% of the microparticle dry mass.

18. A method of claim 16 wherein magnetic substance and said organic compound in totality constitute at least 70% of the microparticle dry mass, or at least 90% of the microparticle dry mass.

19. A method of claim 16 wherein said liquid medium is essentially free of said charged polymer not associated with said magnetic substance.

20. A method of claim 16 wherein said liquid medium comprises water.

21. A method of claim 20 wherein said organic substance is poorly soluble in water.

22. A method of claim 21 wherein said contacting comprises mixing of said magnetic substance dispersed in a water-containing medium with a solution of said organic substance in a medium comprising a water-miscible organic solvent.

23. A method of claim 16 wherein said organic compound is a pharmaceutical, further comprising a step of coating said microparticle with a substance effective to prolong the microparticle blood circulation time.

24. A method of claim 16 further comprising a step of coating said microparticle with a hydrophilic polymer.

25. A method of claim 24 wherein said coating comprises contacting the microparticle with the hydrophilic polymer linked to a hydrophobic moiety.

26. A method of claim 24 wherein said hydrophilic polymer further comprises a targeting moiety.