Biomedical Engineering Reference
In-Depth Information
of commercial products are nanoclay-reinforced thermoplastics, antistatic and conductive carbon-
nanofi ber polymer composites, and silver nanoparticle-incorporated antimicrobial resin coatings.
Similarly, nanoparticles are the major players among nanomaterials in the biomedical fi eld. In
particular, a variety of pore-containing soft colloidal nanoparticles are under extensive study for
application in controlled drug delivery, as outlined in Table 8.1.
In general, drug delivery systems using these pore-containing soft nanoparticles have low toxic-
ity. These systems are especially useful in providing effi cient protection of labile drugs, improved
solubilization for hydrophobic drugs, and encapsulation of water-soluble drugs for increased deliv-
ery suffi ciency and, often, sustained release. In addition to the adjustable nanostructures for more
fl exibility in drug loading and release control, the tunable surface chemistry of the nanoparticles
enables potential self-regulated drug delivery and site-specifi c targeting drug delivery. The high
ratio of surface area to volume present in these nanoparticles provides further increased sensitivity
to surrounding bioenvironmental changes. The small dimensions and the versatile structures of the
nanoparticle-based drug carriers facilitate their penetration through tissues and intravenous circula-
tion and open up the possibility of integrating more sophisticated functions. For example, the deliv-
ery of haloperidol, a neuroleptic drug, using poly(ethylene oxide) (PEO)-containing block copolymer
micelles that are conjugated with cell-specifi c antibodies shows clearly increased therapeutic effect
by selective targeting at brain glial cells.
44
Martin and coworkers demonstrated the precise release
of individual drugs and bioactive molecules from the conductive polymer nanotube-deposited
microelectrode neural probe at desired points in time by using electrical stimulation of conductive
polymer nanotubes (Figures 8.2 and 8.3).
32
The fabrication process involves electrospinning of a drug-
incorporated PLA or PLGA biodegardable polymer on the probe tip, followed by electrochemical
deposition of a poly(3,4-ethylenedioxythiophene) (PEDOT) conducting polymer coating around
the electrospun biodegradable nanofi bers. The drug-incorporated fi ber templates can be removed
or slowly degraded, providing controlled drug delivery. The conducting polymer nanotube-coated
microelectrode neural probes were used in the neural prosthetic devices in the nervous systems and
showed signifi cantly decreased electrode impedance, which is desirable for obtaining high signal-
to-noise ratio because of its well-defi ned internal and external surface textures providing effective
surface area for ionic to electronic charge transfer.
32
Adding to the tailorable morphology and surface chemistry, polymers with interesting proper-
ties provide another dimension of novelty to the nanoporous systems designed for controlled drug
delivery. For instance, environment-sensitive hydrogel has been used in a number of smart drug
delivery systems; in particular, glucose-sensitive hydrogels that undergo a sol-gel phase transition
were used to modulate insulin release. Park and coworkers developed one kind of glucose-sensitive
hydrogel by binding glucose to the hydrogel backbone and mixing the glucose-bound hydrogel
with concanavalin A (Con A), which is a four-valent lectin that can bind glucose.
45
Insulin was
incorporated or trapped in such a composite hydrogel. When the free glucose concentration in the
environment is low, the Con A acts as an effective crosslinker and the cross-linking density of the
hydrogel is suffi ciently high. Thus, the gel pore size is suffi ciently low to restrict insulin diffu-
sion. With increased environmental free glucose concentration, there is a competition between the
bound glucose and the free glucose for the Con A binding sites, resulting in a less effective cross-
linking density of the hydrogel and hence facilitated insulin release. Based on this mechanism,
modulated insulin release was achieved using the glucose-sensitive membrane and matrix systems
(Figure 8.4).
8.2.2 I
NORGANIC
N
ANOSTRUCTURED
P
OROUS
M
ATERIALS
Rigid inorganic porous nanomaterials are the subject of increasing interest as the potential candi-
date carriers for controlled drug delivery. In particular, silicon-based porous nanomaterials appear
to be promising platforms in this category. As in the case of soft porous nanomaterials, the morphol-
ogy and the surface chemistry (thanks to the well-studied silicon chemistry) of silicon-based porous
