Microspheres containing therapeutic agents and related methods of use
View Patent ↗Microspheres, compositions including the microspheres, and methods of using the microspheres are disclosed herein. The microspheres can be substantially spherical and can include a copolymer of a monomer (such as an acrylic monomer) and a cyclodextrin or a derivative thereof. The microspheres can also include a therapeutic agent, such as a platinum-based drug.
1. Microspheres suitable for use in therapeutic embolization, comprising:
a biocompatible, polymeric material comprising a copolymer comprising an acrylamide monomer, wherein the acrylamide monomer is selected from N-[tris(hydroxymethyl)methyl]acrylamide and N,N′-methylenebis(acrylamide), and a cyclodextrin; and
a therapeutic agent;
wherein the microspheres comprise a biodegradable portion and a non-biodegradable portion, wherein the biodegradable portion comprises the cyclodextrin, and wherein the microspheres retain a substantially spherical shape after degradation of the biodegradable portion when placed in a patient's body.
2. The microspheres of claim 1 , wherein the cyclodextrin is functionalized to include a moiety that is polymerizable with said acrylamide monomer.
3. The microspheres of claim 1 , wherein the cyclodextrin is selected from α(alpha)-cyclodextrin, β(beta)-cyclodextrin and γ(gamma)-cyclodextrin and combinations thereof.
4. The microspheres of claim 1 , wherein the cyclodextrin is incorporated into the backbone of the polymer.
5. The microspheres of claim 1 , wherein the polymeric material is cross-linked.
6. The microspheres of claim 1 , wherein the copolymer comprises N-[tris(hydroxymethyl)methyl]acrylamide.
7. The microspheres of claim 1 , wherein the microspheres are one or more of hydrophilic, swellable, and water insoluble.
8. The microspheres of claim 1 , wherein the microspheres have an average diameter of from about 10 μm to about 2000 μm.
9. The microspheres of claim 1 , wherein the therapeutic agent comprises a drug selected from one or more of the following: cisplatin, carboplatin, oxaliplatin, oxiplatin, satraplatin, picoplatin, nedaplatin, triplatin, lipoplatin, spiroplatin, iproplatin, docetaxel and paclitaxel.
10. The microspheres of claim 1 , wherein the microspheres are configured to decrease the flux of blood flow across a region of the vasculature of the patient by 90% or more regardless of whether the biodegradable portion of the microsphere has been degraded.
11. The microspheres of claim 1 , wherein the cyclodextrin is distributed in a substantially uniform manner throughout the microsphere.
12. The microspheres of claim 1 , wherein the cyclodextrin is disposed only on an outer surface of the microspheres.
13. A method of embolization, comprising:
administering to a patient microspheres comprising:
a biocompatible, polymeric material comprising a copolymer comprising an acrylamide monomer, wherein the acrylamide monomer is selected from N-[tris(hydroxymethyl)methyl]acrylamide and N,N′-methylenebis(acrylamide), and a cyclodextrin; and
a therapeutic agent, wherein the therapeutic agent comprises a platinum-based drug, a taxol, an anthracycline, or a campothecin,
wherein the microspheres comprise a biodegradable portion and a non-biodegradable portion, wherein the microspheres retain a substantially spherical shape after degradation of the biodegradable portion when placed in a patient's body;
occluding a blood vessel with the microspheres; and
releasing the therapeutic agent.
14. The method of claim 13 , wherein the copolymer comprises N-[tris(hydroxymethyl)methyl]acrylamide.
15. The method of claim 14 , wherein the therapeutic agent is released by degradation of the cyclodextrin.
16. The method of claim 13 , wherein the therapeutic agent comprises a platinum-based drug selected from one or more of the following: cisplatin, carboplatin, oxaliplatin, oxiplatin, satraplatin, picoplatin, nedaplatin, triplatin, lipoplatin, spiroplatin, and iproplatin.
17. A method of manufacturing microspheres, the method comprising:
obtaining an aqueous solution comprising one or more acrylamide monomers selected from N-[tris(hydroxymethyl)methyl]acrylamide and N,N′-methylenebis(acrylamide), and an olefin-containing cyclodextrin;
obtaining an oil;
mixing the aqueous solution into the oil; and
polymerizing the one or more acrylamide monomers and the olefin-containing cyclodextrin after the aqueous solution has been mixed into the oil; and
isolating microspheres formed by the polymerization of the one or more acrylamide monomers and the olefin-containing cyclodextrin, wherein the microspheres comprise a biodegradable portion and a non-biodegradable portion, and wherein the microspheres are configured to retain a substantially spherical shape after degradation of the biodegradable portion when placed inside a patient's body.
18. The method of claim 13 , wherein the cyclodextrin is functionalized to include a moiety that is polymerizable with said acrylamide monomer.
19. The method of claim 17 , wherein the one or more one or more acrylamide monomers is N-[tris(hydroxymethyl)methyl]acrylamide.