Biomedical Engineering Reference
In-Depth Information
localization and released DNA in the perinuclear zone. Adiponectin plasmid DNA
delivery using nanoparticles resulted in a dose-dependent growth inhibition of
cultured arterial smooth muscle cells. It is concluded that magnetically driven plas-
mid DNA delivery can be achieved using biodegradable nanoparticles containing
oleate-coated magnetite and surface modified with PEI oleate ion-pair complexes
that enable DNA binding. The materials composing the nanoparticles are biodegrad-
able, so they break down into simpler, nontoxic chemicals that can be carried away
in the blood. This addresses the safety concerns of the use of nonbiodegradable
nanoparticles in vivo. As a nonviral method, it avoids the unwanted immune system
responses that have occurred when viruses are used to deliver gene therapy.
Although the research done in cell cultures is in early stages, it may represent a
new method for delivering gene therapy to benefit blood vessels damaged by arterial
disease. Such nanoparticles could be magnetically directed into stents inserted into a
patient's partially blocked vessels to improve blood flow. Delivering antigrowth
genes to stents could help prevent restenosis. The magnetically driven delivery sys-
tem also may find broader use as a vehicle for delivering drugs, genes, or cells to a
target organ. After preloading genetically engineered cells with nanoparticles,
researchers could use magnetic forces to direct the cells to a target organ. Furthermore,
researchers might deliver nanoparticles to magnetically responsive, removable stents
in sites other than blood vessels, such as airways or parts of the gastrointestinal tract.
After the nanoparticles have delivered a sufficient number of genes, cells, or other
agents to have a long-lasting benefit, the stent could be removed.
eNOS Gene Therapy for Restenosis
Endogenous NO in the vasculature is vasoprotective by inhibiting platelet and leu-
kocyte adhesion, inhibiting smooth muscle cell (SMC) proliferation and migration,
and promoting endothelial survival and proliferation. At sites of vascular injury
following angioplasty, the endothelium is disrupted and NO synthesis is impaired.
Hence, augmenting local NO synthesis through eNOS gene transfer may help arrest
the proliferative response to vascular injury. Several experimental studies have
shown that delivery of eNOS gene to balloon-injured rat carotid arteries using viral
as well as nonviral vectors results in reduction in neointimal formation.
The first multicenter, prospective, single-blind, dose escalation study was con-
ducted to obtain safety and tolerability information of the iNOS-lipoplex
(CAR-MP583) gene therapy for reducing restenosis following PCI (von der Leyen
et al.
2011
). Local coronary intramural CAR-MP583 delivery was achieved using the
Infiltrator balloon catheter. There were no complications related to local application
of CAR-MP583. In one patient, PCI procedure-related transient vessel occlusion
occurred with consecutive troponin elevation. There were no signs of inflammatory
responses, hepatic toxicity, or renal toxicity. No dose relationship was seen with
regard to adverse events across the dose groups. It was concluded that coronary
intramural lipoplex-enhanced iNOS gene therapy during PCI is feasible and appears
to be safe. These initial clinical results are encouraging to support further clinical
research, particularly in conjunction with new local drug delivery technologies.
Search WWH ::
Custom Search