Methods of Treatment with Drug Eluting Stents with Prolonged Local Elution Profiles with High Local Concentrations and Low Systemic Concentrations

Abstract

A drug eluting stent can include a stent body having a polymeric coating with a lipophilic and/or hydrophilic element. A drug that has a bioactivity that inhibits cell proliferation can be disposed in the polymeric coating. The drug can be present in the polymer at an amount greater than or equal to about 150 μg/cm 2 . The polymeric coating and drug are configured to cooperate so as to form a diffusion pathway with tissue when the stent is disposed in a body lumen such that the drug preferentially diffuses into the tissue over a body fluid passing through the body lumen such that a maximum systemic blood concentration of the drug is less than about 40 ng/ml.

1 . A method of treating peripheral vascular disease in a subject, the method comprising:
 implanting in a peripheral artery of a subject a drug eluting stent comprising:
 a stent body of about 130 mm to about 170 mm in length, the stent body being a design of annular elements and interconnectors where the annular elements are connected adjacently by at least one interconnector; 
 a polymeric coating disposed on the stent body, the polymeric coating being 2 μm to 50 μm in thickness; and 
 a lipophilic drug disposed in the polymeric coating, the lipophilic drug being present at an amount between about 4 mg to about 8 mg; 
   wherein the maximum systemic blood concentration of the lipophilic drug in the subject is about 30 ng/ml or less than 30 ng/ml.   
     
     
         2 . The method as in  claim 1 , wherein the lipophilic drug is present in an amount greater than or equal to 200 μg/cm 2 . 
     
     
         3 . The method as in  claim 1 , wherein the lipophilic drug is everolimus, zotarolimus, tacrolimus, paclitaxel, or a combination thereof. 
     
     
         4 . The method as in  claim 3 , wherein the lipophilic drug is present at an amount between about 5 mg and about 7 mg. 
     
     
         5 . The method as in  claim 1 , wherein the lipophilic drug is present at an amount between about 5 mg and about 7 mg. 
     
     
         6 . The method as in  claim 1 , wherein the polymeric coating ranges from about 4 μm to about 25 μm in thickness. 
     
     
         7 . The method as in  claim 1 , wherein the polymeric coating comprises a primer layer disposed on the stent body, a drug-loaded layer disposed on the primer layer, and a topcoat layer disposed on the drug-loaded layer. 
     
     
         8 . The method as in  claim 7 , wherein the polymeric coating is characterized by at least one of the following:
 the primer layer being from about 1% to about 20% of the total coating thickness;   the drug-loaded layer being from about 25% to about 90% of the total coating thickness; or   the topcoat being from about 5% to about 50% of the total coating thickness.   
     
     
         9 . The method as in  claim 8 , wherein the stent body is nitinol, the lipophilic drug is everolimus, and the polymer of the polymeric coating is an ethylenevinylalcohol copolymer. 
     
     
         10 . The method as in  claim 1 , wherein the lipophilic drug is everolimus. 
     
     
         11 . The method as in  claim 4 , wherein the lipophilic drug is everolimus. 
     
     
         12 . The method as in  claim 1 , wherein the lipophilic drug is zotarolimus. 
     
     
         13 . The method as in  claim 4 , wherein the lipophilic drug is zotarolimus. 
     
     
         14 . The method as in  claim 1 , wherein the lipophilic drug is paclitaxel. 
     
     
         15 . The method as in  claim 4 , wherein the lipophilic drug is paclitaxel. 
     
     
         16 . The method as in  claim 1 , wherein the maximum systemic blood concentration of the lipophilic drug in the subject is about 20 ng/ml or less than 20 ng/ml. 
     
     
         17 . The method as in  claim 1 , wherein the maximum systemic blood concentration of the lipophilic drug in the subject is about 10 ng/ml or less than 10 ng/ml. 
     
     
         18 . The method as in  claim 1 , wherein the stent body is formed from Nitinol. 
     
     
         19 . The method as in  claim 1 , wherein the peripheral artery of the subject into which the stent is implanted is a superficial femoral artery. 
     
     
         20 . The method as in  claim 1 , wherein the peripheral artery of the subject into which the stent is implanted is an iliofemoral artery.