Drug Delivery to the Cardiovascular System - Applications of Biotechnology in Cardiovascular Therapeutics - page 45

DDS in the Management of Ischemic Heart Disease

Current treatment for ischemic heart disease with pharmaceuticals and revascular-
ization procedures is directed at relief of symptoms and does not treat the underlying
pathophysiologic process. Major approaches to this problem are lysis of the throm-
bus, surgical endarterectomy, dilatation of the stenosed arteries by percutaneous
angioplasty or bypass revascularization procedures. Cell therapy could repair the
myocardial damage following coronary artery occlusion. Gene therapy strategies
could reduce the incidence of heart disease by correcting the gene defects respon-
sible for insulin-dependent diabetes mellitus and hyperlipidemia and hypertension.
Methods of drug delivery for ischemic heart disease are shown in Table 2.5 .
The blood vessels are lined with a monolayer of endothelial cells which main-
tain a crucial role in maintaining blood fluidity and vascular patency. Endothelial
cells generate a number of molecules that protect blood vessels from injury and
major disease processes such as thrombosis and atherosclerosis. The three best
known of these are prostacyclin, tissue plasminogen activator (tPA), and nitric
oxide (NO). Several of these active molecules have been purified or synthesized
and administered systematically for the treatment of arterial thrombotic disor-
ders. For example, intravenous infusion of tPA has been shown to reduce the
morbidity and mortality of coronary heart disease. The disadvantages of this
compound are:

• Bioavailability is limited by neutralization of tPA by plasminogen activator

inhibitor.
Adverse effects such as hemorrhage ensue when large doses are given. •

• It acts selectively at fibrin-generating sites and systemic administration often

does not produce adequate local concentration.

Table 2.5 Drug delivery in ischemic heart disease

Oral administration of sustained and controlled release drugs
Intramuscular injections
Intravenous administration of novel therapies
Thrombolysis
Emulsified formulations of halogenated anesthetics as cardioprotective agents
Intraarterial
Thrombolysis
Local delivery of drugs the site of lesion
Injections into the heart
Transdermal
Nitric oxide-based therapies
Nanoparticle-based drug delivery to the cardiovascular system
Cell therapy
Gene therapy
RNAi