Implantable medical articles having a coating formed of hydrophobic derivatives of natural biodegradable polysaccharides are described. The coatings can include a bioactive agent, and demonstrate desirable bioactive agent release profiles and can be prepared to have high drug loading. The coated implantable medical articles can be used to treat medical conditions, such as those requiring prolonged administration of the bioactive agent at a target location in the body.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graph illustrating elution profiles of stents coated with lidocaine and hydrophobic derivatives of natural biodegradable polysaccharides.
Claims
1. An implantable medical article comprising a biodegradable bioactive-agent releasing coating, the coating comprising a matrix of hydrophobic derivatives of natural biodegradable polysaccharides and bioactive-agent within the matrix, wherein the coating is capable of releasing bioactive agent following placement of the medical article in a subject.
2. The implantable medical article of claim 1 wherein the matrix comprises hydrophobic derivatives having an average molecular weight of 100,000 Da or less.
3. The implantable medical article of claim 2 wherein the matrix comprises hydrophobic derivatives having an average molecular weight of 50,000 Da or less.
4. The implantable medical article of claim 3 wherein the matrix comprises hydrophobic derivatives having an average molecular weight of 25,000 Da or less.
5. The implantable medical article of claim 4 wherein the matrix comprises hydrophobic derivatives having an average molecular weight in the range of 2000 Da to 20,000 Da.
6. The implantable medical article of claim 5 wherein the matrix comprises hydrophobic derivatives having an average molecular weight in the range of 4000 Da to 10,000 Da.
7. The implantable medical article of claim 1 wherein the hydrophobic derivatives comprise a poly-α(1→4)glucopyranose backbone.
8. The implantable medical article of claim 1 wherein the hydrophobic derivatives comprise a plurality of groups pendent from a polysaccharide backbone, the groups comprising a hydrocarbon segment selected from the group consisting of linear, branched, and cyclic C2-C18 groups.
9. The implantable medical article of claim 8 wherein the hydrocarbon segment is selected from the group consisting of linear, branched, and cyclic C4-C10 groups.
10. The implantable medical article of claim 9 wherein the hydrocarbon segment is selected from the group consisting of linear, branched, or cyclic C5-C7 groups.
11. The implantable medical article of claim 10 wherein the plurality of groups pendent from the polysaccharide backbone provide a degree of substitution in the range of 2-3.
12. The implantable medical article of claim 11 wherein the hydrocarbon segment is a C6 aromatic group.
13. The implantable medical article of claim 9 wherein the hydrocarbon segment is selected from the group consisting of branched C4-C10 alkyl groups.
14. The implantable medical article of claim 13 wherein the plurality of groups pendent from the polysaccharide backbone provide a degree of substitution in the range of 0.5-1.5.
15. The implantable medical article of claim 1 wherein the hydrophobic derivatives have a Tg of 35° C. or greater.
16. The implantable medical article of claim 15 wherein the hydrophobic derivatives have a Tg in the range of 40° C. to 90° C.
17. The implantable medical article of claim 1 wherein the hydrophobic derivatives are present in the coating in an amount in the range of 35 wt % to 90 wt %.
18. The implantable medical article of claim 17 wherein the hydrophobic derivatives are present in the coating in an amount in the range of 35 wt % to 60 wt %.
19. The implantable medical article of claim 1 wherein the bioactive agent is present in the coating in an amount in the range of 10 wt % to 65 wt %.
20. The implantable medical article of claim 1 wherein the coating is formed on the surface of an implantable ocular device.
21. The implantable medical article of claim 1 wherein the coating is formed on the surface of an implantable intravascular device.
22. The implantable medical article of claim 1 wherein the bioactive agent is coupled to a polysaccharide backbone of the hydrophobic derivatives via a hydrolyzable ester bond.
23. The implantable medical article of claim 1 wherein the coating further comprises a biocompatible hydrophilic polymer.
24. The implantable medical article of claim 23 wherein the biocompatible hydrophilic polymer is selected from the group consisting of group consisting of poly(ethylene glycol), hydrophilic polysaccharides, polyvinyl pyrrolidones, polyvinyl alcohols, low molecular weight methyl cellulose, hydroxypropyl methyl cellulose (HPMC).
25. A method for delivering a bioactive agent to a subject comprising steps of:
implanting at a target site in a subject an implantable medical article comprising a biodegradable bioactive-agent releasing coating, the coating comprising a matrix of hydrophobic derivatives of natural biodegradable polysaccharides and bioactive agent within the matrix, andallowing the bioactive agent to be released from the coating in the subject following the step of implanting.
26. The method of claim 25 wherein the step of implanting comprises delivering the article to a portion of the eye.
27. The method of claim 25 wherein the step of allowing, the bioactive agent released comprises a carboxylate group.
28. The method of claim 25 wherein the bioactive agent is coupled to a polysaccharide backbone of the hydrophobic derivatives via a hydrolyzable ester bond.
29. A method for preparing a biodegradable bioactive-agent releasing coating on a medical article comprising steps of:
preparing a coating composition comprising hydrophobic derivatives of natural biodegradable polysaccharides and bioactive-agent; andapplying the coating composition on a surface of a medical article to form a coating, wherein the bioactive-agent is capable of being released from the coating following implantation of the medical article in a subject.
Patent Application
20070218102
