Thermoresponsive Nisopropylacrylamide Based Nanogels For Dermal Drug Delivery.

PhDStimuli 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 efficientl