Drug Delivery to the Cardiovascular System - Applications of Biotechnology in Cardiovascular Therapeutics - page 54

Table 2.6 Drug delivery for peripheral arterial disorders
Oral sustained and controlled release preparations
Delivery of thrombolytic agent to the clot through an arterial catheter
Delivery of growth factors to promote angiogenesis in ischemic limbs
Drug-eluting stents
Transdermal
Immune modulation therapy
Nitric oxide-based therapy
Antisense therapy
Cell therapy
Gene therapy
Alteplase solutions have been analyzed following delivery through the AngioJet
Xpeedior rheolytic thrombectomy device to characterize the viability of proteins
exposed to high shear stress (Semba et al. 2005 ). No significant fragmentation or
aggregation of protein was observed. Alteplase solutions, when delivered through
the AngioJet Xpeedior rheolytic thrombectomy device, remain stable and biologically
active in vitro. This method needs to be tested clinically.
Drug Delivery for Peripheral Arterial Disease
Various methods for drug delivery for peripheral arterial disorders (PADs) are listed
in Table 2.6 . Cholesterol-lowering and antihypertensive therapies also improve PAD.
Delivery of Thrombolytic Agent to the Clot Through a Catheter
Alfimeprase (ARCA) is an enzyme produced by recombinant DNA technology. It is
a thrombolytic agent that is intended to directly degrade fibrin when delivered
through an arterial catheter to the site of a blood clot. It directly degrades fibrin, a
protein that provides the scaffolding for blood clots. In clinical studies, this direct
mechanism of action has been shown to provide rapid clot dissolution with a well-
tolerated safety profile. Alfimeprase's thrombolytic activity is localized to the site of
delivery because it is rapidly inactivated by a-2 macroglobulin, a naturally occur-
ring protein in the blood, as it moves away from the site of delivery and into the
general blood circulation. This clearance mechanism focuses the thrombolytic activ-
ity to the site of the clot and offers the potential to minimize bleeding side effects.
It is in phase III clinical trials for the treatment of peripheral arterial occlusion.
Delivery of Growth Factors to Promote Angiogenesis in Ischemic Limbs
Therapeutic vascularization remains a significant challenge in regenerative medi-
cine applications, where the goal is to induce vascular growth in ischemic tissue or
scale up tissue-engineered constructs. Engineered PEG-based bioartificial hydrogel