Microspheres for active embolization
The present invention relates to injectable compositions comprising biocompatible, swellable, substantially hydrophilic, non-toxic and substantially spherical polymeric material carriers which are capable of efficiently delivering bioactive therapeutic factor(s) for use in embolization drug therapy. The present invention further relates to methods of embolization gene therapy, particularly for the treatment of angiogenic and non-angiogenic-dependent diseases, using the injectable compositions.
1. An MRI-detectable, substantially spherical microsphere suitable for active embolization, comprising:
an iron oxide particle;
a biocompatible, hydrophilic, non-biodegradable polymeric material, wherein the polymeric material comprises an acrylamide moiety and an ionic moiety; and
an anti-neoplastic agent, wherein the anti-neoplastic agent is associated with the polymeric material by an ionic interaction with the ionic moiety.
2. The microsphere of claim 1 , wherein the anti-neoplastic agent is selected from at least one of doxorubicin, epirubicin or irinotecan.
3. The microsphere of claim 1 , wherein the microsphere is cross-linked.
4. The microsphere of claim 3 , wherein the cross-linking agent is N,N-methylene-bis-acrylamide.
5. The microsphere of claim 1 , wherein the polymeric material comprises a copolymer comprising:
an acrylate polymer or a polyvinyl polymer, and
an acrylamide polymer.
6. The microsphere of claim 5 , wherein the acrylamide polymer comprises N-tris-hydroxymethyl methylacrylamide.
7. The microsphere of claim 1 , wherein the iron oxide particle is selected from at least one of: iron(II) oxide, iron(III) oxide, or mixtures thereof.
8. The microsphere of claim 1 , wherein the iron oxide particle is a nanoparticle.
9. The microsphere of claim 1 wherein the microspheres are swellable and wherein the diameter of the microsphere ranges from about 10 μm to about 1000 μm before swelling.
10. The microsphere of claim 9 , wherein the diameter of the microsphere ranges from about 30 μm to about 2000 μm after swelling.
11. An injectable composition comprising the microsphere of claim 1 and a biocompatible carrier, wherein the composition is sterile.
12. The composition of claim 11 where the composition is injectable through a needle of about 18 gauge or smaller.
13. A method for active embolization, comprising administering to a patient an MRI-detectable, substantially spherical microsphere comprising:
an iron oxide particle;
a biocompatible, hydrophilic, non-biodegradable polymeric material, wherein the polymeric material comprises an acrylamide moiety and an ionic moiety; and
a positively-charged drug, wherein the positively-charged drug is associated with the polymeric material by an ionic interaction with the ionic moiety.
14. The method of claim 13 , wherein the drug is an anti-neoplastic agent.
15. The method of claim 14 , wherein the drug is doxorubicin.
16. The method of claim 13 , wherein administering to a patient comprises injecting a composition comprising the microsphere and a biocompatible carrier, wherein the composition is sterile.
17. The method of claim 16 , wherein the composition is injectable through a needle of about 18 gauge or smaller.
18. The method of claim 13 , wherein the microsphere is cross-linked.
19. The method of claim 18 , wherein the cross-linking agent is N,N-methylene-bis-acrylamide.
20. The method of claim 13 , wherein the polymeric material comprises a copolymer comprising:
an acrylate polymer or a polyvinyl polymer, and
an acrylamide polymer.
21. The method of claim 20 , wherein the acrylamide polymer comprises N-tris-hydroxymethyl methylacrylamide.
22. The method of claim 13 , wherein the iron oxide particle is selected from at least one of: iron(II) oxide, iron(III) oxide, or mixtures thereof.
23. The method of claim 13 , wherein the iron oxide particle is a nanoparticle.
24. The method of claim 13 wherein the microspheres are swellable and wherein the diameter of the microsphere ranges from about 10 μm to about 1000 μm before swelling.
25. The method of claim 24 , wherein the diameter of the microsphere ranges from about 30 μm to about 2000 μm after swelling.