Prevention and treatment of restenosis by local administration of drug

Abstract

Apolipoprotein A-I (ApoA-I), preferably a variant form such as Apolipoprotein A-I Milano (ApoA-IM), alone or more preferably in combination with a lipid carrier such as phospholipids or other drug, can be administered locally before or during bypass surgery on diseased coronary, peripheral, and cerebral arteries, surgery to implant grafts or transplanted organs, or angioplasty, or to stabilize unstable plaques. In an alternative embodiment, the apolipoprotein is not provided directly, but the gene encoding the apolipoprotein is provided. The gene is introduced into the blood vessel in a manner similar to that used for the protein, where the protein is then expressed. The technique can also be used for delivery of genes for treatment or prevention or restenosis or other cardiovascular diseases. In yet another embodiment, stents are coated with apolipoproteins alone, apolipoproteins formulated with lipids, genetically engineered cells expressing the apolipoproteins, naked DNA coding for an apolipoprotein, or other drugs such as anti-proliferatives for local delivery to an injury site. In a preferred embodiment, the system is used with combination therapy, with for local delivery of an agent such as an apolipoprotein in combination with systemic anti-hypertension therapy, anti-inflammatoy therapy, lipid regulation and/or anti-coagulation therapy. These treatments can begin prior to, concurrent with or following local delivery.