Drug Delivery to the Cardiovascular System - Applications of Biotechnology in Cardiovascular Therapeutics - page 46

Intravenous Emulsified Formulations of Halogenated Anesthetics
Preconditioning against myocardial infarction by inhalation of volatile anesthetics
is well known. New emulsified formulations of halogenated anesthetics adminis-
tered intravenously reduce myocardial infarct size when administered before pro-
longed ischemia and reperfusion in experimental animals. Lipid vehicle in the
formulation produces transient increases in heart rate, whereas emulsified volatile
anesthetics had no effect on hemodynamics before coronary occlusion. Emulsified
isoflurane, enflurane, and sevoflurane reduce infarct size of the area at risk.
Administration of lipid vehicle or emulsified sevoflurane does not produce sedation
or respiratory depression in conscious rabbits. It is concluded that intravenous
emulsified halogenated anesthetics produce acute and delayed preconditioning
against myocardial infarction.
Injectable Peptide Nanofibers for Myocardial Ischemia
Endothelial cells can protect cardiomyocytes from injury through platelet-derived
growth factor (PDGF)-BB signaling. PDGF-BB induces cardiomyocyte Akt phos-
phorylation in a time- and dose-dependent manner and prevents apoptosis via
PI3K/Akt signaling. An experimental study in rats using injectable self-assembling
peptide nanofibers, which bound PDGF-BB in vitro, demonstrated sustained delivery
of PDGF-BB to the myocardium at the injected sites for 14 days (Hsieh et al. 2006 ).
This blinded and randomized rat study showed that injecting nanofibers with
PDGF-BB, but not nanofibers or PDGF-BB alone, decreased cardiomyocyte death
and preserved systolic function after myocardial infarction. A separate blinded and
randomized study showed that PDGF-BB delivered with nanofibers decreased infarct
size after ischemia/reperfusion. PDGF-BB with nanofibers induced PDGFR-b and
Akt phosphorylation in cardiomyocytes in vivo. These data demonstrate that
PDGF-BB signaling and the in vitro finding can be translated into an effective
in vivo method of protecting myocardium after infarction. Furthermore, this study
shows that injectable nanofibers allow precise and sustained delivery of proteins to
the myocardium with potential therapeutic benefits.
Delivery of Angiogenesis-Inducing Agents for Myocardial Ischemia
Angiogenesis therapy is aimed at revascularization of the myocardium in ischemic
heart disease. Surgical procedures involve implantation of blood vessels. Medical
therapy is mainly by use of growth factors such as VEGF, FGF, and placental
growth factor (PIGF). These are proteins given by injection. Growth factors deliv-
ered by gene therapy include VEGF, FGF-4, HGF, Del-1, and HIF-1. Cell therapy
for myocardial ischemia involves implantation of various types of cells including
hematopoietic stem cells that are engineered to produce angiogeneic agents. Routes
of administration include intravenous injection, intracoronary infusion, and percu-
taneous intramyocardial delivery.