Prospects for site-specific delivery of pharmacologic and molecular therapies

Department of Medicine (Cardiology), St. Elizabeth's Hospital, Tufts University School of Medicine, Boston, Massachusetts 02135.

The local delivery of therapeutic agents to the arterial wall represents a new strategy for the treatment of vascular diseases, including restenosis. Approaches for local, intravascular, site-specific delivery include 1) direct deposition of therapeutic agents into the vessel wall through an intravascular delivery system; 2) systemic administration of inactive agents followed by local activation; and 3) systemic administration of fusion toxins that have a specific affinity to proliferating smooth muscle cells at the angioplasty site. In addition to conventional drugs, new therapeutic agents based on molecular mechanisms, including recombinant genes and antisense oligonucleotides, are now under investigation. Although development of intravascular drug delivery devices, including those tailored to accommodate novel therapeutic agents, offers new treatment options for restenosis and other vascular diseases, certain issues that currently limit the safety and efficacy of these approaches remain to be addressed.

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