Treatment of restenosis by controlled-release delivery systems of tyrphostins

Percutaneous transluminal coronary angioplasty (PTCA) procedures include ba lloon dilation, excisional atherectomy, endoluminal stenting, and laser abl ation. However, despite significant advances in reducing the acute complica tions of percutaneous revascularization procedures with premedications and better techniques, chronic restenosis of dilated lesions remains a serious and frequent problem. The neointimal formation is dependent on smooth muscl e cells and most probably fibroblast proliferation and migration mediated b y various cytokines and growth factors. The unsuccessful attempts to contro l restenosis by systemic pharmacological interventions have prompted many r esearchers to look for more promising therapeutic approaches such as local drug delivery. In this review we discuss the rationale for local drug deliv ery based on restenosis pathophysiology, local drug delivery approaches, th e rationale for antiproliferative therapy, and review the in vitro and in v ivo studies of local drug delivery systems of tyrphostins (protein tyrosine kinase inhibitors) in restenosis therapy. (C) 2000 Wiley-Liss, Inc.