Biomedical Engineering Reference
In-Depth Information
A better and safer approach in addressing RES uptake and clearance was
the modification of the NP surface to include hydrophilic blockers such as
PEG as well as block copolymers in the tetronic and pluronic families of
surfactants. These modifications significantly altered the biodistribution of
liposomes and biopolymers since liver and splenic uptake of these hydrated
particles was marginal. In addition, these preparations were shown to passively
accumulate in solid tumors through extravasation of the leaky vasculature that
fed them. 140,141 Unfortunately, blockers such as PEG-based stabilizers, includ-
ing carbowax, or block copolymers such as poloxamine or poloxamer 53,140,141
failed to alter the biodistribution of the cAu-TNF vector when compared to the
cAu-TNF vector alone which may be explained due to an inability of the tumor
necrosis factor (TNF)-saturated gold particles to directly bind the hydrophilic
blockers. Thus, such poorly bound blockers were unable to stop the vectors'
uptake by the RES.
5.9   VARIOUS NM s  FOR DRUG DELIVERY
It is a well-known fact that radiotherapy- and chemotherapy-based cancer treat-
ments affect both tumors and healthy tissue, thereby leading to sometimes toxic
side effects. Using biocompatible NPs, cancer immunotherapy attempts to spe-
cifically deliver the drugs or the treatment to the affected tissues/cells as well as
to enhance the natural immune response to tumor cells. Aside from treatment of
cancers, NM-based drug delivery systems can also be used to deliver vaccines
and drugs for other diseases that are hard to reach.
5.9.1   Polymers
Polymeric NPs made from natural and synthetic polymers have received the
majority of attention due to their stability and ease of surface modification. 113,142
These can be configured to achieve controlled drug release and tissue/cell spe-
cific localization at the site of the disease by tuning the polymer characteristics,
surface chemistry, and functionalization. 8,10,49,143
Nanopolymers carrying drugs can become concentrated preferentially to
tumors, inflammatory sites, and at antigen sampling sites by virtue of the EPR
effect of the vasculature. 1 Once at the target site, biodegradable polymeric NPs
can act as a drug depot that provides a continuous supply of encapsulated thera-
peutic compounds at the disease site such as at solid tumors.
Polymeric drug delivery systems can be used to provide targeted (cellular
or tissue) delivery of drugs with improved bioavailability enabling sustained
release of drugs or solubilization of drugs for systemic delivery. This system
can be adapted to protect therapeutic agents against enzymatic degradation (i.e.
nucleases and proteases). 144 The use of biodegradable materials for NP prepara-
tion allows for sustained drug release within the target site over a period of days
or even weeks. Biodegradable NPs formulated from polylactic glycolic acid
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