Drug Delivery to the Cardiovascular System - Applications of Biotechnology in Cardiovascular Therapeutics - page 30

Table 2.1 Routes of drug delivery used for treatment of cardiovascular disorders
Systemic administration of drugs by various routes (non-targeted)
Oral
Intramuscular
Intravenous
Transdermal
Sublingual
Inhalation
Systemic administration for targeted effect
Local administration
Drug delivery into the myocardium: direct intramyocardial injection, drug-eluting implanted devices
Drug delivery via coronary venous system
Injection into coronary arteries via cardiac catheter
Intrapericardial drug delivery
Release of drugs into arterial lumen from drug-eluting stents
Local intramyocardial delivery (IMD) is under active clinical investigation for
cell therapies to treat congestive heart failure (CHF), and gene therapies to induce
revascularization of ischemic myocardium in coronary artery disease. Locally
delivered agents can migrate away from the site of delivery through pathways that
include lymphatics. Postdelivery redistribution can be observed using fluorescent
tracers of different physical geometries. This approach provides a means to charac-
terize these pathways and to delineate their importance in local cardiovascular drug
delivery. Animal experimental studies show that IMD may provide a means to
administer hydrophilic agents to the periadventitial zone of the arterial wall to limit
restenosis (Altman et al. 2003 ). The lack of redistribution of the 15 mm micro-
spheres supports the potential for cells to remain localized to the site of administra-
tion for an extended period of time.
Erythropoietin (EPO) protects myocardium against ischemic injury, but it also
produces polycythemia, which can cause thromboembolic complications. Following
induction of myocardial infarction in rats, local sustained delivery by intramyocar-
dial injection of EPO combined with hydrogel has been shown to enhance the
cardioprotective effect without causing polycythemia (Wang et al. 2009 ). The
hydrogel allows sustained release of EPO, which inhibits cell apoptosis and
increases angiogenesis that subsequently reduces infarct size and improves cardiac
function without apparent adverse effects.
Drug Delivery via Coronary Venous System
Retrograde coronary venous perfusion can preserve myocardium during experi-
mental coronary artery occlusion and has been used clinically to deliver oxygenated