Biomedical Engineering Reference
In-Depth Information
various types of NPs can induce different inflammatory reactions. For ex-
ample, single-walled carbon nanotubes are more toxic in inducing epithe-
lioid granuloma [90]. Mixed carbon NPs and nanotubes are able to induce
platelet aggregation in vitro and accelerate the rate of vascular thrombosis
in rat carotid artery [91]. In CNS, neutral NPs and low concentrations of
anionic NPs have no effect on BBB integrity, whereas high concentrations
of anionic NPs and cationic NPs are toxic for BBB. NPs seem to stimulate
the production of reactive oxygen species and oxidative stress [92]. After
absorption, NPs distribute to various organs, tissues, and cells. Only a few
recent studies have focused on in vivo biodistribution of engineered NPs as
it relates to the nanostructure's physical parameters. In studies with quan-
tum dots and single-walled carbon nanotubes, it was discovered that a high
dose of the quantum dots is sequestered in the liver, and the percentage
of these NPs dose sequestered is dependent upon the surface modification
[93]. Although targeted NPs have emerged as one strategy to overcome the
lack of specificity of conventional chemotherapy, there are other potential
risks and challenges associated with this novel strategy. Some cancer cell
types would develop drug resistance, rendering drugs released from the tar-
geted NPs to be ineffective. Also the targeted NPs might change the stabil-
ity, solubility, and pharmacokinetic properties of the carried drugs. The shelf
life, aggregation, leakage, and toxicity of materials used to make NPs are
other limitations for their use. Some materials used to make NPs show low
toxicity, but degrade quickly and do not circulate in tissues long enough for
sustained drug/gene delivery. On the other hand, other materials such as
carbon nanotubes and quantum dots are durable and can persist in the body
for weeks, months, or even years, making them potentially toxic and limiting
their use for repeated treatments. New materials to make targeted NPs such
as silicon/silica (solid, porous, and hollow silicon NPs) have been developed.
However, their use for drug delivery to cancer patients has taken off slowly
due to the potential health risks associated with introducing new materials
in the human body. A systematic quantitative analysis of the pharmacokinet-
ics (absorption, distribution, metabolism, and excretion) of NPs, can lead
to improvements in the design of NPs for diagnostic and therapeutic ap-
plications, a better understanding of nanostructures non-specificity toward
tissues and cell types, and assessments of basic distribution and clearance,
that serve as the basis in determining their toxicity and future investigative
directions. Besides developing new materials and selecting appropriate ma-
terials for each specific treatment, other factors need to be optimally selected
in order to design better targeted NPs. These factors include the particles
size, shape, sedimentation, drug encapsulation efficacy, desired drug release
profiles, distribution in the body, circulation, and cost. Despite extensive re-
search efforts to develop new targeted NPs, only a few of them are in clinical
use including Abraxane®, Doxil®, and Myocet
TM
, and are approved by the
FDA. A major contributor to the slow development of effective targeted
