Elastin-based copolymers

Abstract

A copolymer comprising a block of an elastin pentapeptide and method of making and using the copolymer are provided.

1 .- 40 . (canceled) 
     
     
         41 . A method of forming a coating comprising an elastin-based copolymer on a medical device, comprising
 providing a solution comprising the elastin-based copolymer,   applying the solution to the medical device to form a layer of the solution on the medical device, and   treating the medical device with heat at a temperature about 15° C. to about 30° C. above the lower critical solution temperature (LCST) of the elastin-based copolymer to form the coating.   
     
     
         42 . The method of  claim 41 , wherein the solution comprises about 5% to about 30% the elastin-based copolymer. 
     
     
         43 . The method of  claim 41 , wherein the solution comprises about 10% to about 20% the elastin-based copolymer. 
     
     
         44 . The method of  claim 41 , wherein the solution comprises a solvent selected from the group consisting of water, dimethylformamide (DMF), dimethyl suloxide (DMSO), dimethyl acetamide (DMAC), methyl ethyl ketone (MEK), ethylene glycol, triflouroethanol (TFE), and combinations thereof. 
     
     
         45 . The method of  claim 41 , wherein the solution comprises a bioactive agent. 
     
     
         46 . The method of  claim 45 , wherein the bioactive agent is selected from the group consisting of paclitaxel, docetaxel, estradiol, 17-beta-estradiol, nitric oxide donors, super oxide dismutases, super oxide dismutase mimics, 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO), tacrolimus, dexamethasone, rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin (everolimus), 40-O-(3-hydroxy)propyl-rapamycin, 40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, 40-O-tetrazole-rapamycin, 40-epi-(N1-tetrazolyl)-rapamycin (ABT-578), γ-hiridun, clobetasol, mometasone, pimecrolimus, imatinib mesylate, midostaurin, and combinations thereof. 
     
     
         47 . The method of  claim 41 , wherein the block copolymer comprising a block comprising an elastin pentapeptide (A) and a hydrophilic block (B), wherein the elastin pentapeptide is VGVPG (SEQ ID NO: 1). 
     
     
         48 . The method of  claim 47 , wherein the block copolymer is an ABA type triblock copolymer. 
     
     
         49 . The method of  claim 47 , wherein the hydrophilic block comprises lysine. 
     
     
         50 . The method of  claim 47 , wherein the hydrophilic block comprises a synthetic polymer. 
     
     
         51 . The method of  claim 47 , wherein the hydrophilic block comprises a natural polymer. 
     
     
         52 . The method of  claim 47 , wherein the hydrophilic block is a variant of the VGVPG (SEQ ID NO: 1). 
     
     
         53 . The method of  claim 49 , further comprising a phosphoryl choline (PC) or poly(ethylene glycol) (PEG) pendant group, wherein the PC or PEG is conjugated to the block copolymer via lysine in the hydrophilic block. 
     
     
         54 . The method of  claim 50 , wherein the synthetic polymer is selected from the group consisting of PEG, PVP (polyvinylpyrrolidinone), polyacrylamide, poly(PEG acrylate), poly(HEMA), poly(acrylic acid), and combinations thereof. 
     
     
         55 . The method of  claim 51 , wherein the natural polymer is selected from the group consisting of collagen or collagen derivative, hyaluronic acid, alginate, and combinations thereof. 
     
     
         56 . The method of  claim 47 , wherein the block copolymer further comprises a sequence that promotes proliferation and/or migration of endothelial cells. 
     
     
         57 . The method of  claim 56 , wherein the sequence is selected from the group consisting of RGD, cRGD, SIKVAV (SEQ ID NO: 2), CNP, YIGSRG (SEQ ID NO: 3), mimetics thereof, and combinations of thereof. 
     
     
         58 . The method of  claim 47 , wherein the block copolymer further comprises a biodegradable linkage between the A and B blocks. 
     
     
         59 . The method of  claim 58 , wherein the biodegradable linkage is selected from the group consisting of poly(lactic acid) (PLA), poly(glycolic acid) (PLGA), polycaprolactone (PCL), poly(3-hydroxybutyric acid (PHB), poly(4-hydroxybutyrate (P4HB), and combinations thereof. 
     
     
         60 . The method of  claim 41 , wherein the medical device is a stent. 
     
     
         61 . The method of  claim 60 , wherein the stent is a bioabsorbable stent.