The use of nanomaterials for biomedical applications is an
emerging and important field. This is particularly true of
advancements in targeted and controlled drug delivery, which
offer several important improvements over traditional drug
administration. The clinical efficacy of small-molecule
therapeutics is currently limited by many factors, including:
poor solubility, inefficient cellular uptake, overly rapid renal
clearance and an inability to target only desired locations such
as diseased tissues. The use of nanocarriers for drug delivery
may greatly improve the efficacy over traditional therapeutics by
lowering the total dosage, limiting the exposure to affected
areas only, and giving greater temporal control over drug
elution. These materials often make use of both organic and
inorganic components, exploiting the unique and useful properties
of each constituent to achieve novel, synergistic functions.
This dissertation presents a study of nanocomposites comprising
the three most important materials in this field: titania, iron
oxides and polypyrrole. Titania is a strong photocatalyst, iron
oxides provide useful responses to applied magnetic fields, and
polypyrrole is a polymer with unique electrochemical properties.
Studies in this dissertation were aimed at combining these three
materials to create a novel structure that is responsive towards
light, magnetic fields and electrical stimulation to serve as an
enabling platform for the loading and release of biologically
interesting compounds.
These nanomaterials have been paired with amino acids L-lysine
and L-glutamic acid, two organic molecules of interest due to
their ability to bind to DNA and proteins, and to form prodrugs
that exhibit enhanced performance compared to traditionally
administered medicines. Two model compounds have been loaded and
released on these carriers: Ketoprofen, an important
anti-inflammatory that is traditionally hindered by its limited
cellular uptake levels; and fluorescein isothiocyanate, a
fluorescent dye molecule that is a common tool used in this field
for nanocarrier location and easy visualisation of
release-related kinetics.
First, an investigation into the effect of pH on the binding of
amino acids to titania, iron oxide and polypyrrole is presented
with a view towards optimising the functionalised material for
subsequent loading and release of the model drugs (in this case,
amine-reactive molecules). The release mechanism of
photo-activated TiO2 is studied in detail with a particular focus
on the competition between the cleavage of bonds versus organic
degradation on the catalystโs surface. Both mechanisms are
currently reported in literature and studies were aimed at
identifying the more dominant pathway in the system developed
alongside understanding the crucial role of reaction time scales
on this photochemistry.
Then, the pH-tuneable flocculation of the amino
acid-functionalised nanoparticles via electrostatic attractions
is exploited to create a novel, anisotropic assembly of iron
oxides. These filaments display a dynamic and unique response
towards a rotating magnetic field by creating local microscale
vortices. This motion is used to enhance local delivery rate of
molecules through magnetic-field triggered microscale mixing.
Finally, this anisotropic iron oxide structure is combined with
polypyrrole to create a unique, novel material that possesses
directional conductivity, a photothermal response, and magnetic
field-triggered release of loaded molecules at enhanced and
controllable rates compared with traditional diffusion-limited
systems