Biomedical Engineering Reference
In-Depth Information
Figure 4-1
Drug encapsulation in a nanocarrier.
molecules can be released from nanocarriers in a controlled manner over
time to maintain a drug concentration within a therapeutic window or the
release can be triggered by some stimulus unique to the delivery site [32].
The surface of the nanocarrier can be engineered to increase the blood circu-
lation half-life and influence the bio-distribution, while attachment of tar-
geting ligands to the surface can result in enhanced uptake by target tissues.
The net result of these properties is to lower the systemic toxicity of the
therapeutic agent, while increasing the concentration of the agent in the area
of interest, resulting in a higher therapeutic index for the therapeutic agent.
In addition to therapeutic drugs, imaging agents can also incorporated into
nanocarriers to improve tumor detection and imaging [33]. Finally, nano-
particles can be engineered to be multifunctional with the ability to target
diseased tissue, carry imaging agents for detection, and deliver multiple
therapeutic agents for combination therapy [34]. The NPs penetrate easily
in the neoangiogenic vessels interstitium, Fig. 4-2 remaining entrapped in
the tumor, with evident higher retention times of drug into tumor. NPs may
be delivered to specific sites by size-dependent passive targeting or by active
targeting. Passive targeting is directly linked to intrinsic cancer cellular and
micro-environmental features. Active targeting involves the use of peripher-
ally conjugated targeting moieties for enhanced delivery of NP systems. This
method has been performed to obtain a high degree of selectivity to specific
tissues and to enhance the uptake of NPs into cancer cells and angiogenic
microcapillaries. With these strategies, NPs drug delivering systems mini-
mize the uptake and the toxic side effects of the anticancer agent by nor-
mal cells and enhance the entry and accumulation of the drug into tumor
cells. NPs behavior within the biological microenvironment, stability, and
extracellular and cellular distribution varies with their chemical makeup,
