Device for in vivo delivery of bioactive agents and method of manufacture thereof

Abstract

The drug eluting device consists of an implantable structural element for in vivo controlled delivery of bioactive active agents to a situs in a body. The implantable structural element may be configured as an implantable prosthesis, such as an endoluminal stent, cardiac valve, osteal implant or the like, which serves a dual function of being prosthetic and a carrier for a bioactive agent. Control over elution of the bioactive agents occurs through a plurality of cantilever-like cover members which prevent drug elution until an endogenous or exogenous stimulus causes the cover members to open and permit drug elution.

What is claimed is: 
     
         1 . A method of making a drug-eluting medical device, comprising the steps of:
 a) Vacuum depositing a first layer of a biocompatible material onto a substrate;   b) Vacuum deposing a sacrificial layer of material onto the first layer of a biocompatible material;   c) Removing portions of the sacrificial layer to form internal chamber defining regions of the sacrificial layer;   d) Vacuum depositing a second layer of biocompatible material onto the internal chamber defining regions of the sacrificial layer and the first layer of biocompatible material;   e) Forming at least one of a plurality of openings passing through the second layer of biocompatible and communicating with the internal chamber defining regions of the sacrificial layer;   f) Removing the internal chamber defining regions of the sacrificial layer thereby forming at least one of a plurality of internal chambers residing entirely between the first layer of biocompatible material and the second layer of biocompatible material; and   g) Disposing at least one of a plurality of cover members covering the at least one of a plurality of openings, the at least one of a plurality of cover members having a first position which covers at least one of the plurality of openings and a second position which uncovers at least one of the plurality of openings.   
     
     
         2 . The method according to  claim 1 , wherein the vacuum depositing steps further comprise at least one of physical vapor deposition and chemical vapor deposition. 
     
     
         3 . The method according to  claim 1 , wherein step (g) is conducted before step (a) and step and further comprises the step of vacuum depositing the first layer of biocompatible material onto the plurality of cover members. 
     
     
         4 . The method according to  claim 1 , further comprising the step of loading at least one bioactive agent into the at least one of a plurality of internal chambers. 
     
     
         5 . The method according to  claim 4 , further comprising the step of selecting the at least one bioactive agent from the group of pharmacologically active antibiotic drugs, antiviral drugs, neoplastic agents, steroids, fibronectin, anti-clotting drugs, anti-platelet function drugs, drugs which prevent smooth muscle cell growth on inner surface wall of vessel, heparin, heparin fragments, aspirin, coumadin, tissue plasminogen activator, urokinase, hirudin, streptokinase, antiproliferative agents, antioxidants, antimetabolites, thromboxane inhibitors, non-steroidal and steroidal anti-inflammatory drugs, immunosuppresents, beta and calcium channel blockers, genetic materials including DNA and RNA fragments, complete expression genes, antibodies, lymphokines, growth factors, vascular endothelial growth factor, fibroblast growth factor, prostaglandins, leukotrienes, laminin, elastin, collagen, nitric oxide, integrins, paclitaxel, taxol, rapamycin, rapamycin derivatives and analogues, sirolimus, rapamune, tacrolimus, dexamethasone, everolimus, ABT-578 and growth factors. 
     
     
         6 . The method of  claim 1 , wherein at least one of the first layer of biocompatible material, the second layer of biocompatible material and the at least one of a plurality of cover members further comprise a thin metallic film. 
     
     
         7 . The method of  claim 1 , wherein the plurality of cover members are in the first position in their native state and transition to the second position upon application of a stimulus. 
     
     
         8 . The method of  claim 1 , wherein the drug-eluting device is selected from the group consisting of stent, covered stents and vascular grafts. 
     
     
         9 . The method of  claim 1 , wherein the first layer of biocompatible material, the second layer of biocompatible material and the at least one of a plurality of cover members further comprise further comprise a material selected from the group consisting of titanium, vanadium, aluminum, nickel, tantalum, zirconium, chromium, silver, gold, silicon, magnesium, niobium, scandium, platinum, cobalt, palladium, manganese, molybdenum and alloys thereof, zirconium-titanium-tantalum alloys, nickel titanium alloy, chromium-cobalt alloy, and stainless steel.