Insertable medical devices having microparticulate-associated elastic substrates and methods for drug delivery

• US 20090246252A1
• Filed: 03/27/2009
• Published: 10/01/2009
• Est. Priority Date: 03/28/2008
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Arps, James Howard, Bach, Andrew G.
• Granted Patent: US 8,951,545 B2
• Time in Patent Office: Days
• US Class Current: 424/425
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 2300/622 Microcapsules
• CPC Class Codes: A61L 29/041 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 29/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 2025/1004 Balloons with folds, e.g. folded or multifolded
• CPC Class Codes: A61M 2025/1031 Surface processing of balloon members, e.g. coating or deposition; Mounting additional parts onto the balloon member's surface
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 2025/1075 having a balloon composed of several layers, e.g. by coating or embedding
• CPC Class Codes: A61M 25/1002 characterised by balloon shape A61M25/1006, A61M25/1009 take precedence
• CPC Class Codes: A61M 25/104 used for angioplasty
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 3/02 : Starch; Degradation products thereof, e.g. dextrin

Abstract

The present invention provides insertable medical devices having elastic surfaces associated with bioactive agent-containing microparticulates and a coating material. Upon expansion of the elastic surfaces the microparticulates can be released to a subject.

Claims

1. An insertable medical device capable of delivering a bioactive agent to a subject, the device comprising:

an expandable elastic portion,

a coating comprising a flexible hydrogel matrix on the expandable elastic portion, and

microparticulates associated with the flexible hydrogel matrix, the microparticulates comprising a bioactive agent, wherein a portion of the microparticulates associated with the coating are capable of becoming disassociated from the coating upon expansion of the elastic portion in the subject.

2. The device of claim 1 wherein the majority of the associated microparticulates are non-homogenously distributed in the flexible hydrogel matrix, and partially embedded in the flexible hydrogel matrix at its surface.

3. The device of claim 1 wherein the flexible hydrogel matrix comprises a polymer selected from the group consisting of poly(acrylamide), poly(methacrylamide), poly(vinylpyrrolidone), poly(acrylic acid), poly(ethylene glycol), poly(vinyl alcohol), poly(HEMA), methyl vinyl ether/maleic anhydride copolymers, and vinyl pyrrolidone/(meth)acrylamide copolymers.

4. The device of claim 1 wherein flexible hydrogel matrix comprises a polymer having pendent reacted photogroups that covalently bond the polymer to a target selected from other polymers in the coating and a surface of the expandable elastic portion.

5. The device of claim 1, wherein the expandable elastic portion is all or a portion of a balloon.

6. The device of claim 5, wherein the balloon is an angioplasty balloon.

7. The device of claim 1, wherein the coating has a thickness in the range of 5 μ

m to 100 μ

m.

8. The device of claim 1, wherein the microparticulates have an average greatest dimension in the range of 0.1 μ

m to 10 μ

m.

9. The device of claim 1, wherein the microparticulates are in neat form.

10. The device of claim 1, wherein the bioactive agent is selected from the group consisting of antiproliferatives, antiinflamatories, and antiplatelet compounds.

11. The device of claim 10, wherein the bioactive agent is paclitaxel

12. The device of claim 1, formed by a process including a step of disposing a liquid composition with dissolved bioactive agent on the flexible hydrogel matrix and allowing microparticulates to form on, and become partially embedded in the flexible hydrogel matrix.

13. A method for delivering a bioactive agent to a subject comprising the steps of

providing an insertable medical device comprising:

an expandable elastic portion,

a coating comprising a flexible hydrogel matrix on the expandable elastic portion, and

microparticulates associated with the flexible hydrogel matrix, the microparticulates comprising a bioactive agent;

inserting the medical device into a subject, and

expanding the expandable elastic portion in the subject, wherein a portion of the microparticulates become disassociated from the coating and released into the subject, and wherein bioactive agent is released from the microparticulates to provide a therapeutic effect to the subject.

14. The method of claim 13, wherein an amount of microparticulate in the range of 10% to 100% of the microparticulates associated with the elastic portion or coating are released from the device upon expansion of the elastic portion.

15. An insertable medical device capable of delivering a bioactive agent to a subject, the device comprising:

an expandable elastic portion,

a coating comprising a biodegradable polymeric matrix on the expandable elastic portion, and

microparticulates associated with the biodegradable polymeric matrix, the microparticulates comprising a bioactive agent, wherein at least a portion

of the biodegradable matrix with associated microparticulates are capable of becoming delaminated from the elastic portion upon expansion of the elastic portion in the subject.

16. The device of claim 15 wherein the biodegradable polymeric matrix comprises a biodegradable polymer selected from polylactide, polygylcolide, polydioxanone, poly(lactide-co-glycolide), poly(glycolide-co-polydioxanone), polyanhydrides, poly(glycolide-co-trimethylene carbonate), and poly(glycolide-co-caprolactone), biodegradable poly(ester-amides), biodegradable polyetherester copolymers, biodegradable ester-containing block copolymers, degradable dextran-based polymers, and degradable maltodexrin-based polymers.

17. The device of claim 15 comprising a flexible hydrogel matrix between the expandable elastic portion and the biodegradable polymeric matrix.

18. The device of claim 15 wherein biodegradable polymeric matrix comprises a biodegradable polymer having pendent polymerized groups that crosslink the biodegradable polymers together to form the matrix.

19. The device of claim 15, wherein the coating has a thickness in the range of 5 μ

m to 100 μ

m.

20. The device of claim 15 wherein the biodegradable polymeric matrix comprises a degradable maltodexrin-based polymer.

21. The device of claim 15 wherein the biodegradable polymeric matrix is capable of fracturing and then becoming delaminated from the elastic portion upon expansion of the elastic portion in the subject.

22. The device of claim 15 wherein the biodegradable coating is non-contiguous.

23. A method for delivering a bioactive agent to a subject comprising the steps of

providing an insertable medical device comprising:

an expandable elastic portion,

a coating comprising a biodegradable polymeric matrix on the expandable elastic portion, and

microparticulates associated with the biodegradable polymeric matrix, the microparticulates comprising a bioactive agent;

inserting the medical device into a subject, and

expanding the elastic portion in the subject, wherein the biodegradable polymeric matrix fractures into fractured matrix portions, and some or all of the fractured matrix portions delaminates from the elastic surface and is transferred to tissue with the associated entrapped microparticulates, and the bioactive agent is then released from the microparticulates to provide a therapeutic effect to the subject.