Local delivery of therapeutics for percutaneous coronary intervention

Percutaneous coronary intervention (PCI) has become a highly effective alternative for the treatment of coronary artery disease. The use of stents has reduced the rates of restenosis by preventing elastic recoil and negative remodeling, however neointima formation still remains an issue. Local drug delivery is an attractive option to maintain effective drug concentrations at the site of arterial injury without risking systemic toxicity. Drug-eluting stents (DESs) are implanted to provide local drug delivery to combat neointima formation by slowing cell proliferation and migration. However, problems still remain with DES use including the non-specificity of therapeutics, incomplete endothelialization leading to late thrombosis, necessity for longer term anti-platelet drug use, and local hypersensitivity to polymer delivery matrices. This review describes recent advances in local drug delivery for the prevention of restenosis. Many different drug therapeutics have been considered, as well as the material properties of the drug delivery systems. Systems for delivery include DESs, balloon catheters, polymeric cuffs and nanoparticles. Our own experience designing a controlled release device for a new therapeutic agent, Serp-1, an anti-inflammatory protein, is briefly presented. The release of Serp-1 can be extended using diffusion controlled release from physically crosslinked poly(vinyl alcohol) hydrogels, where its release properties can be tuned by the processing parameters of the hydrogel.