Poly(tetrafluoroethylene) polymer with nitric oxide donating surface

Abstract

Described herein are nitric oxide (NO)-donating poly(tetrafluoroethylene) (PTFE) polymers and polymer surfaces and methods of making and using the same. The NO-donating PTFE polymers can be used to fabricate at least a portion of an implantable medical device, coat at least a portion of an implantable medical device or form at least a portion of an implantable medical device. The NO-donating PTFE polymers provide controlled release of NO once implanted at or within the target site.

1 . A nitric oxide donating polymer comprising:
 a poly(tetrafluoroethylene) polymer having the structure:   
       
         
           
           
               
               
           
         
         wherein n is an integer between 1 and 25,000 and wherein each of R 1 , R 2 , R 3 , and R 4  is independently fluorine or a tertiary amine having the structure 
       
       
         
           
           
               
               
           
         
         wherein X 1  and X 2  are each independently O or not present, Y 1  and Y 2  are each independently selected from C 1  to C 10  alkyl, C 1  to C 10  alkenyl, C 1  to C 10  alkynyl, C 3  to C 8  cyclic alkyl, or any combination thereof, and each of B 1 , B 2 , B 3 , B 4 , B 5 , and B 6  is independently hydrogen or a diazeniumdiolate (DD) group, with the proviso that at least one of B 1 , B 2 , B 3 , B 4 , B 5 , and B 6  is a DD group; 
         wherein at least one of R 1 , R 2 , R 3 , and R 4  is a tertiary amine of the structure of Formula 2 
       
     
     
         2 . The nitric oxide donating polymer of  claim 1  wherein Y 1  and Y 2  are —(CH 2 )—. 
     
     
         3 . The nitric oxide donating polymer of  claim 1  wherein said polymer is associated with an implantable medical device. 
     
     
         4 . The nitric oxide donating polymer of  claim 1  wherein said implantable medical device is selected from the group consisting of stents, catheters, micro-particles, probes, vascular grafts, and combinations thereof. 
     
     
         5 . The nitric oxide donating polymer of  claim 1 , wherein said polymer comprises one or more bioactive agents other than the nitric oxide. 
     
     
         6 . The nitric oxide donating polymer of  claim 5 , wherein said at least one bioactive agent is selected from the group consisting of anti-proliferatives, estrogens, chaperone inhibitors, protease inhibitors, protein-tyrosine kinase inhibitors, leptomycin B, peroxisome proliferator-activated receptor gamma ligands (PPARγ), hypothemycin, bisphosphonates, epidermal growth factor inhibitors, antibodies, proteasome inhibitors, antibiotics, anti-inflammatories, anti-sense nucleotides and transforming nucleic acids, cytostatic compounds, toxic compounds, chemotherapeutic agents, analgesics, antibiotics, protease inhibitors, statins, nucleic acids, polypeptides, growth factors and delivery vectors, and liposomes.