Injectable superparamagnetic nanoparticles for treatment by hyperthermia and use for forming an hyperthermic implant

• US 20090081122A1
• Filed: 05/23/2005
• Published: 03/26/2009
• Est. Priority Date: 05/23/2005
• Status: Abandoned Application

• Current Assignee: Ecole Polytechnique Federal de Lausanne, Hopitaux Universitaires De Geneve, Universite de Geneve
• Original Assignee: Ecole Polytechnique Federal de Lausanne, Hopitaux Universitaires De Geneve, Universite de Geneve
• Inventors: Petri-Fink, Alke, Doelker, Eric, Rufenacht, Daniel, Chastellain, Mathiew, Jordan, Olivier, Hofmann, Heinrich
• Application Number:
  US11/918,927
• Publication Number:
  US 20090081122A1
• Time in Patent Office: Days
• US Class Current: 424/1.290
• CPC Class Codes: A61K 41/0052 Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The injectable formulation for treatment by hyperthermia comprises a liquid carrier and heat-generating superparamagnetic iron oxide nanoparticles having a mean diameter not greater than 20 nm. Said injectable formulation is able to form in-situ a hyperthermic solid or semi-solid implant upon contact with a body fluid or tissue. Said hyperthermic solid or semi-solid implant may be useful for treating a tumor or a degenerative disc disease by hyperthermia.

Claims

1-22. -22. (canceled)

23. An injectable formulation for treatment by hyperthermia comprising

a liquid carrier which is based on anyone of a precipitating polymer solution in water-miscible solvent, an in-situ polymerizing or crosslinking compound, a thermosetting compound and an hydrogel, and

heat-generating superparamagnetic iron oxide nanoparticles having a mean diameter not greater than 20 nm,

said injectable formulation being able to form in-situ an hyperthermic solid or semi-solid implant upon contact with a body fluid or tissue.

24. The injectable formulation according to claim 23, wherein the heat-generating superparamagnetic iron oxide nanoparticles have a mean diameter ranging from 5 to 15 nm.

25. The injectable formulation according to claim 24, wherein the heat-generating superparamagnetic iron oxide nanoparticles have a span of 1 or less, said span being defined as span=d90%−

d10%/d50%, wherein d90%. d10% and D50% are the nanoparticle sizes in diameters, and the given percentage value is the percentage of particles smaller than that size.

26. The injectable formulation according to claim 23, wherein the heat-generating superparamagnetic iron oxide nanoparticles are maghemite nanoparticles, magnetite nanoparticles or a mixture thereof.

27. The injectable formulation according to claim 23, wherein the heat-generating superparamagnetic iron oxide nanoparticles have a non-spherical shape.

28. The injectable formulation according to claim 27, wherein the heat-generating superparamagnetic iron oxide nanoparticles have a diameter ratio of the larger diameter to the smaller diameter ranging from 1 to 3.

29. The injectable formulation according to claim 23, wherein the heat-generating superparamagnetic iron oxide nanoparticles are coated with a biocompatible polymer.

30. The injectable formulation according to claim 23, wherein the heat-generating superparamagnetic iron oxide nanoparticles are immobilized in organic or inorganic beads.

31. The injectable formulation according to claim 30, wherein the heat-generating superparamagnetic iron oxide nanoparticles are immobilized in silica beads.

32. The injectable formulation according to claim 31, wherein the silica beads immobilizing the heat-generating superparamagnetic iron oxide nanoparticles have a mean diameter ranging from 20 nm to 1 μ

m.

33. The injectable formulation according to claim 32, wherein the silica beads immobilizing the heat-generating superparamagnetic iron oxide nanoparticles have a mean diameter ranging from 300 nm to 800 nm.

34. The injectable formulation according to claim 31, wherein the iron oxide nanoparticles-containing silica beads are further coated with a biocompatible polymer.

35. The injectable formulation according to claim 23, wherein the liquid carrier is based on a precipitating polymer solution in water-miscible solvent consisting in a solution of a preformed polymer in an organic solvent which is able to precipitate in the tissue following exchange of the solvent with surrounding physiological water, thus being able to produce a polymer cast filling the tissue.

36. The injectable formulation according to claim 23, which further comprises a radiopacifier.

37. The injectable formulation according to claim 23, wherein the liquid carrier is based on a radiopaque polymer.

38. The injectable formulation according to claim 23, which further comprises drugs or biopharmaceuticals.

39. Use of an injectable formulation as defined in claim 23, for forming in-situ an hyperthermic solid or semi-solid implant.

40. Use of an injectable formulation according to claim 39, for forming in-situ an hyperthermic solid or semi-solid implant for treating a tumor.

41. Use of an injectable formulation according to claim 39, for forming in-situ an hyperthermic solid or semi-solid implant for treating a degenerative disc disease.

42. An hyperthermic solid or semi-solid implant, said implant being formed in-situ upon contact of the injectable formulation as defined in claim 23 with a body fluid or tissue, when said injectable formulation is injected into a body.

43. Use of an hyperthermic solid or semi-solid implant according to claim 42 for the treatment of a tumor.

44. Use of an hyperthermic solid or semi-solid implant according to claim 42 for the treatment of a degenerative disc.

45. A method for treating a tumor, which comprises forming in-situ a hyperthermic solid or semi-solid implant according to claim 42, and subjecting the hyperthermic solid or semi-solid implant to a heating procedure.

46. A process for preparing iron oxide nanoparticles-containing silica beads for use in the injectable formulation according to claim 31, said process comprising the steps of:

flocculating iron oxide nanoparticles in the presence of a controlled amount of poly(vinyl alcohol)(PVA) in order to give aggregates of iron oxide nanoparticles, reacting said aggregates of iron oxide nanoparticles with a silica precursor in order to give iron oxide nanoparticles-containing silica beads.

47. The injectable formulation according to claim 35, wherein the liquid carrier is based on a radiopaque polymer.