| dc.description.abstract | Stimuli responsive polymers offer potential applications as drug delivery
systems. This thesis has focused on thermoresponsive N-isopropylacrylamidebased
nanogels, known to undergo a volume phase transition at a specific
temperature depending on their chemical composition, and their potential
application in dermal drug delivery.
The first results and discussion chapter of this thesis presents the synthesis and
characterisation of NIPAM nanogels, prepared with cross-linkers, and
comonomers designed to introduce charges. The influence of the different
polymerisation parameters on the morphology and physicochemical
characteristics of the nanogels is described and evaluated. NIPAM nanogels of
less than 40 nm in size were obtained and fine-tuned to respond to
temperatures of around 35ºC, i.e. skin temperature. The nanogels were
covalently linked with a fluorescent naphtalimide derivative, which was
shown not to alter the properties of the polymers significantly. Drug uploading
and in vitro release studies at different temperatures using flufenamic acid as
the model drug are presented and discussed.
The second results and discussion chapter describes the biological studies, in
which the labelled drug carriers were tested for skin irritation, using the Zein
protein test, cytotoxicity to and internalisation in keratinocyte cells, followed
by evaluation of skin permeability properties, using excised human skin.
The data presented in this thesis demonstrate that NIPAM nanogels crosslinked
with methylenebisacrylamide can be fine-tuned to respond to a
temperature suitable for dermal applications. The nanoparticles, even when
labelled with fluorescent tags or charged comonomers are non-cytotoxic when
internalised by keratinocytes. When permeation enhancers are used, the
nanogels are able to cross the skin barrier to deliver the drug efficiently | en_US |
