The field of nanomedicine has witnessed an incredible expansion, from a total market value in 2003 of $500 million expected to rise to $160 billion by 2015 (Global Industry Analysts, Inc.). The nanomedicine industry is forecasted to grow and have a significant impact on the economy, with sectors such as biomaterials, diagnostics and drug delivery expected to play a major role. This thesis gives a detailed account of the synthesis and characterisation of molecularly imprinted nanogels for drug delivery. Their toxicity and potential use as a targeted carrier to cancerous cells is evaluated. Initially an overview of nanomaterials and their uses in many areas such as agriculture, energy storage and technology are discussed. The impact of nanomaterials on the life sciences is examined; in particular their application in drug delivery is focussed upon. Chapters 2, 3 and 4 make up the results and discussion of this work. Chapter 2 focuses on developing the synthesis of the acrylamide based nanogels and, vitally, incorporating a suitable fluorescent tag in order to track the nanogels in vitro and in vivo. Fundamentally toxicity studies carried out on the nanogels, both in vitro and in vivo in Danio rerio (zebrafish) are reported in Chapter 3 to ensure the nanogels are biocompatible. Chapter 4 introduces an innovative approach, molecular imprinting, to incorporating a drug into the nanogels. The upload and release of Tamoxifen (a drug used to treat breast cancer) at reduced pH, was also analysed. Finally future development of the carrier is discussed and key issues that need to be addressed.

There is a growing interest in micro sized vehicles with the function of storing, targeting and controlled releasing of substances during the past few decades. However, delivering the desired drugs inside micro containers to living cells is a particular challenging topic of material science. Microcapsules made of polyelectrolyte multilayers exhibit low- or non-toxicity, appropriate mechanical stability, variable degradation and can incorporate remotely addressable release mechanisms in responding to stimuli and external triggering, making them well suitable for targeted drug delivery to live cells. This study investigates interactions between microcapsules made of synthetic (i.e. PSS/PAH) or natural (i.e. DS/PArg) polyelectrolyte and cells, with particular focus on the effect of the glycocalyx layer on the intake of microcapsules by human umbilical vein endothelial cells (HUVECs). Neuraminidase cleaves N-acetyl neuraminic acid residues of glycoproteins and targets the sialic acid component of the glycocalyx on the cell membrane. Three-dimensional CLSM images reveal that microcapsules functionalized with neuraminidase can be internalized by endothelial cells, whereas ones without neuraminidase are blocked by the glycocalyx layer. Uptake of the microcapsules is most significant in the first 2 hours. Following their internalization by endothelial cells, biodegradable DS/PArg capsules rupture by day 5, however, there is no obvious change in the shape and integrity of PSS/PAH capsules within the period of observation. Results from the study support our hypothesis that the glycocalyx functions as an endothelium barrier to cross membrane movement of microcapsules. Neuraminidase-loaded microcapsules can enter endothelial cells by cleaving the glycocalyx in their close proximity with minimum disruption of the glycocalyx layer, therefore they have high potential to act as drug delivery carriers to pass through the endothelium barrier of blood vessels into the surrounding tissue.

Yes / This mini-review highlights the latest advances in the chemistry and biology of Pluronic® triblock copolymers. We focus on their applications in medicine, as drug delivery carriers, biological response modifiers, and pharmaceutical ingredients. Examples of drug delivery systems and formulations currently in clinical use, clinical trials or preclinical development are highlighted. We also discuss the role that Pluronic® copolymers may play in the innovative design of new nanomedicines in the near future. / We thank the Leverhulme Trust (Early Career Fellowship no. ECF-2013-414 to NPEB), the University of Warwick (Grant no. RDF 2013-14 to NPEB) and EPSRC (EP/G004897/1 to APB) for support.