Thermoplastic elastomer is one of the priority polymeric compound identified for promotion and further development, given the growing demand for a number of commercial industries such as automobile, construction, footwear, healthcare, medical and food packaging sectors. In this study polypropylene (PP)/ethylene propylene diene monomer (EPDM) based thermoplastic elastomers are preferred for improving their properties as it can serve as a good replacement for PP or EPDM material, bridging the gap between thermoset and thermoplastic materials. This study focuses to develop PP/EPDM which can resist changes or improve properties when exposed to E-beam radiation, as E-beam also offers sustainable sterilization at low cost. The PP/EPDM blends with mixing ratios of 80/20, 50/50 and 20/80 were melt blended with the process parameters optimized using Design of experiments (DOE). The effect of E-beam on mechanical properties, thermal stability, crystallization and dynamic mechanical properties over the dose of 0 to 100 kGy were studied. The blends with high EPDM content (20PP/80EPDM) showed improvement in tensile strength up to 36% (at 40kGy and 60kGy) and resistant to impact strength up to 100 kGy, at the expense of elongation at break. On the other hand, the blends with high PP content (80 PP/20 EPDM and 50 PP/50 EPDM) showed detrimental effects on mechanical properties at all radiation dose studied and found to be not compatible for E-beam sterilization. Further, ethylene vinyl acetate (EVA) was incorporated to PP/EPDM blends at 10EVA/40EPDM/50PP, 20EVA/30 EPDM/50PP, 30EVA/20 EPDM/50PP and 40EVA/10 EPDM/50PP ratios. The gel content analysis showed that the efficiency of crosslinking decreased with increase in EVA loading. However, the presence of EVA in ternary blend especially facilitated the induction of sufficient crosslinks leading to improvement in tensile strength (up to 29% at 60 kGy), impact strength (up to 15% at 80 kGy) and retention of stiffness and thermal properties under radiation at the expense of elongation at break. In order to develop antibacterial ternary blends, silver nanoparticles (AgNP) were added by varying the loading from 0.3wt% to 1wt%. The Ag-ternary blends showed enhancement in impact properties (up to 9%) at the expense of decrement in tensile properties due to the agglomeration of AgNP. When, exposed to E-beam radiation, the mechanical and thermal properties exhibited similar trend of increment and decrement across radiation dose similar to the blends without AgNP. While, 1% Ag blend composites showed bacteriostatic effect on Staphylococcus aureuson, no significant reduction of Pseudomonas aeruginosa bacteria was observed. All the blends, before and after sterilization showed no significant toxicity on HaCaT cells investigated using in vitro analysis. Thus, the blends showed an instinct that their application could be extended to manufacturing of healthcare products and food packaging sector, as they are biocompatible and can withstand E-beam sterilization as demanded by the respective application. Among all the blends ternary blends studied (that exhibited biocompatibility even after radiation), 20EVA/30EPDM/50PP without AgNP showed the highest tensile strength of 18.41 MPa and impact strength of 43.64 J/m. Only a slight increase in tensile and impact properties was witnessed upon addition of 20% EVA to PP/EPDM blend in comparison to the binary blend (50PP/50EPDM blend). However, unlike the binary blend (whose properties decreased upon radiation), the ternary blend (20EVA/30EPDM/50PP) showed improvement in tensile strength up to 29% at 60kGy and up to 15% increase in impact strength at 80kGy.

Commercial polymers are typically classified according to their melt flow indices, measures of their viscosities. These properties are known to depend on a material’s molar mass distribution, on its averages and its degree of polydispersity. In determining a polymer’s performance, both the molar mass distribution and the process employed to produce the part are highly relevant, since the balance in the mass fractions from its distribution will determine the flow characteristics in the mould, and influence the material’s performance. The compromise polymer manufacturers have to make is to maintain the mechanical properties known to improve with increased molar mass at the same time as a sufficiently low viscosity, known to reduce with decreasing molar mass, to enable part production. This is often achieved by judicious blending of homopolymers. This thesis examines how varying molar mass and distribution in blends leads to changes in the thermal, rheological, and mechanical properties in polystyrene, and discusses and develops physical models to capturing the observed experimental responses. Chromatographic and calorimetric studies were carried out on monodisperse, bimodal blends of monodisperse, polydisperse, and blends of polydisperse polystyrenes. They revealed that changes in molar mass distributions and glass transition temperatures, Tg, could be directly attributed to the blending procedure of choice. In polydisperse blends, higher contents of low molar mass fractions, and corresponding lower Tgs were observed in the blends produced using a melt mixing method compared with solution-blended equivalents. Thermal degradation, accelerated by the large number of chain ends, was suggested as the cause for the increase in low molar mass fractions in the melt-mixed blends. The filtration and precipitation stages characteristic of solution blending instead promoted oligomer loss and evaporation, resulting in reductions in the low molar mass tails of the distributions. Craze initiation stress was measured in 3-point bending isochronal creep tests on the same polymers and blends, and was found to in-crease rapidly with additions of a higher molar mass component, reaching a plateau at 20 wt%. A simple model based on a weighted addition of the crazing stress contributions of individual weight fractions was developed from an established piecewise linear crazing law in order to enable predictions of the crazing stress in the blends, using a power law exponent of 2.59 (90% CI [1.75 17.34]). In highly poly-disperse systems, where short unentangled chains dilute the polymer, it was necessary to include dynamic tube dilution theory. Dilution leads to a change in the entanglement length and hence in the molar mass at which transitions in the crazing mechanisms (disentanglement and chain scission) occur. With the improved model, crazing stress could be predicted even for highly polydisperse blends with wide and bimodal distributions. Linear and non-linear rheological measurements were carried out in shear and extensions on the same materials. Existing rheological models for linear viscoelasticity including Likhtman-McLeish (L-M), Rubinstein-Colby (R-C) and polydisperse double reptation (pDR) theory were applied to the linear experimental data, exposing some of the fundamental difficulties of modelling the structure of systems where multiple chain-lengths interact. R-C was found applicable to bi-modal blends of monodisperse, whereas pDR was better able to model broad polydisperse blends. New non-linear shear and extensional rheology was recorded experimentally on all polymers and blends, and should enable future non-linear theories to be compared to experiment.

Fibre Reinforced Plastics offer several advantages over other materials such as decreased part counts, weight savings, and flexibility. The obstacles to the further expansion of composites use, particularly in cost-conscious industries such as the car industry, include volume, cost, and quality. Liquid Composite Moulding, where the dry textile reinforcement is shaped prior to application of the plastic matrix, offers to address these drivers by offering potential for automation, speed, and quality control. However, the preforming of the dry reinforcement is rarely automated, and its results are variable and hard to predict or control. This thesis aims to facilitate better preforming process design and control. The dominant deformation mechanism that allows reinforcements to conform to a 3D surface is trellis shear. Work is therefore presented on shear characterisation of textile reinforcements using the picture frame and the bias extension tests. Several approaches to normalising these tests to achieve method-independent shear data are proposed, and compared. Of these, a normalisation technique for the bias extension test based on energy considerations appears to be the most appropriate. A constitutive modelling approach, based on the meso-mechanical deformation mechanisms identified in the reinforcement, is developed for characterising the asymmetric shear properties exhibited by non-crimp fabrics. The results from this model are compared with experimental data. Finally, an energy minimising kinematic drape method is developed to account for the use of automated reinforcement blank-holders, and methods for modelling process variability using the code are investigated.

Naturally, bones have a remarkable capacity to regenerate in case of minor injury and continuously remodel throughout an adult life. However, major injuries involving the load bearing bones, such as spine, hips and knee, require orthopaedic surgeries. These bone implants are made from biomaterials. As a result, this study investigates the use of biomaterials such as poly-lactic acid (PLA), nanohydroxyapatite (NHA) and graphene nanoplatelets (GNP) for applications related to bone implants. In this study, NHA was synthesised using precipitation method assisted with ultrasonication. The process parameters (reaction temperature, ultrasonic time and amplitude) were optimised using response surface methodology (RSM) based on 3 factors and 5 level central composite design (CCD). Upon characterisation, the synthesised NHA was confirmed to mimic the HA present in the human bone both chemically and morphologically. The synthesised NHA was then compounded with PLA matrix via melt-mixing by varying the NHA loading (1-5wt%). The impact strength of the PLA-NHA nanocomposites increased with NHA loading, attaining 21.6% enhancement in comparison to neat PLA. In contrast, the tensile strength and modulus of the PLA-NHA nanocomposites exhibited an initial increase of 0.7% and 10.6%, respectively, for 1wt% NHA loading, but deteriorated with the increasing NHA loading. The FESEM microstructures of the impact fractured samples also depicted agglomeration of NHA particles and poor interfacial adhesion between NHA and PLA. Hence, to improve the dispersion, NHA was surface modified (mNHA) using three different surface modifiers namely, 3-aminopropyl triethoxysilane (APTES), sodium n-dodecyl sulfate (SDS) and poly-ethylenimine (PEI). The FESEM analysis revealed an improved interfacial adhesion between PLA matrix and mNHA(APTES), which, enhanced the mechanical, thermal and dynamic mechanical properties of the PLA-5wt%mNHA(APTES). Meanwhile, mNHA(SDS) and mNHA (PEI) had no significant effect on interfacial adhesion, ultimately, failing to improve the properties of the PLA-5wt%mNHA(SDS) and PLA-5wt%mNHA (PEI), respectively. GNP was added into the mNHA in order to further improve the properties of the PLA-5wt%mNHA(APTES) nanocomposite. With the addition of only 0.01wt% of GNP, the impact strength of the PLA-mNHA-GNP nanocomposite was increased by 22.1% (neat PLA) and 7.9% (PLA-5wt%mNHA(APTES)). Nonetheless, the tensile strength recorded a drop of 8.7% (neat PLA) and 9.7% (PLA-5wt%mNHA(APTES)). It is important to note the tensile strength obtained for the PLA-mNHA-GNP nanocomposite was within the acceptable limit of bone strength requirements. Biocompatibility of the nanocomposites (PLA, PLA-NHA, PLA-mNHA and PLA-mNHA-GNP) was investigated using in-vitro analysis. The results show the MG63 cells adhere and grow well on the nanocomposites. Moreover, the nanocomposites encouraged the cells to proliferate and differentiate within 7 days and 21 days of incubation period, respectively. Thus, the in-vitro analysis evidenced the prepared nanocomposites were biocompatible with the MG63 cells. Finally, possible extensions and future works for these prepared nanocomposites as bone implants have been highlighted.

Liquid Composite Moulding (LCM) processes are identified as one of the most potentially advantageous manufacturing routes. The challenge currently is to increase their reliability and expand their applicability. To that end, it was perceived that there was a lack of an advanced integrated simulation tool for the manufacture of three-dimensional, multi-layer textile composites. The tools for the analyses of fabric forming and subsequent flow during LCM processes were simple and immature, with the latter suitable to describe flow in thin structures only. Another noted deficiency was that the simulations provided a single answer to any given problem. Industrial experience has shown that during mould filling, due to the nature of statistical variation in the material properties, the filling patterns and arising cycle times are rarely the same between a given set of identical mouldings. This thesis focuses on permeability prediction of textile reinforcements for LCM processes. The issue of textile variability was also explored through the use of the permeability models' predictive capability. Two novel and efficient numerical approaches were developed to predict textile permeability based on the fabric architecture. The objective was to reduce the complexity of the flow domain and hence provide a faster method to fully characterise the permeability of a textile. Within a wider context, these models were implemented within an integrated modelling framework encompassing draping, compaction and impregnation, based on the TexGen textile schema. TexGen is a generic geometric textile modeller that can be used to create a wide range of textile models. Several validation studies were performed using a range of reinforcements including woven and non-crimp fabrics. A stochastic analysis technique was developed to account for the effect of material variability on permeability. The study based on this technique provided important insights into permeability variations. It was shown that the permeability distribution is a strong function of the textile architecture. The permeability models developed from this work can be used to account for the effects of fabric shear/compaction and statistical variations on permeability. These predicted permeability data can complement experimental data in order to enhance flow simulations at the component scale.

The electrical properties of sulfonated polyaniline (SPAN) and polyaniline (PANI) grown on both conventional (100) and high Miller index GaAs surfaces are investigated. These devices were electrically characterized using Current-Voltage (I-V), Capacitance-Voltage (C-V), Capacitance-Frequency (C-F), Capacitance-Conductance-Frequency (C-G-F), Deep Level Transient Spectroscopy (DLTS), and Laplace DLTS measurements in the temperature range 20 – 440 K. Electrically active defects are generated at/near the interface and away from the interface with energy levels deep in the bandgap of the materials. These defects considerably affect the electrical and optical properties of the devices. This thesis reports the effect of n-type GaAs substrate orientation, namely (100), (311)A and (311)B, on the electrical properties of sulfonated polyaniline (SPAN)/GaAs heterojunction devices. It was found that the interface state density (Dit) of SPAN/(311)B GaAs samples is lower than that of (100) and (311)A GaAs devices. This behaviour is attributed to the effect of crystallographic orientation of the substrates, and was confirmed by DLTS results as well. In addition, the inhomogeneity of the interface between various GaAs substrates and SPAN is investigated in terms of barrier height and ideality factor by performing I–V measurements at different temperatures (20–420 K). The I–V results indicate that the value of the rectification ratio (IF/IR) at 0.5 V is higher for SPAN/(311)B GaAs samples than for SPAN/(100) GaAs and SPAN/(311)A GaAs samples. Moreover, the barrier height decreases and the ideality factor increases with decreasing temperature for all three heterostructure devices. This thesis also reports an extensive study of the electrical properties of PANI/GaAs (organic-inorganic) hybrid heterojunctions. Polyaniline (PANI) thin films were deposited by a very simple technique on (100), (311)A and (311)B ntype Gallium Arsenide (GaAs) substrates to fabricate hybrid devices with excellent electrical properties. The DLTS and Laplace DLTS measurements illustrated that the number of defects at/very close to the interface region in PANI/(311)A GaAs samples is lower than those of PANI/(100) GaAs and PANI/(311)B GaAs samples. Moreover, the analysis of I–V characteristics based on the thermionic emission mechanism has shown a decrease of the barrier height and an increase of the ideality factor at lower temperatures for all the three hybrid devices. The interface states were analysed by series resistance obtained using the C–G–V methods. The interface state density (Dit) of PANI/(100) GaAs devices is approximately one and two order of magnitude higher than that of PANI/(311)B GaAs and PANI/(311)A GaAs devices, respectively. Additionally, the devices show excellent air stability, with rectification ratio values almost unaltered after two years of storage under ambient conditions, making the polyaniline an interesting conductor polymer for future devices applications.

This thesis presents two models for optimizing and guiding the micro injection moulding process. The models are generated by the use of a mathematical procedure, an understanding of the process, and empirical data obtained from several sets of experiments. Micro injection moulding is a well-known process that is heavily used in the mass production of micro polymer parts. It is a very reliable process and apart from the initial investment required for manufacturing a mould, the process is very low cost. Furthermore, polymer developments have led to the process being suitable for the production of micro parts in equipment used in several industries such as medical, automotive, aerospace and sensing. Due to these important industrial applications, several quality criteria have been the subject of research in recent years. One of the main challenges in micro moulding is the modelling of the process in terms of polymer flow and accuracy. This is because current available models use PVT data (pressure, volume, temperature) that is used for modelling of conventional injection moulding. Furthermore, these models ignore several factors in micro moulding such as the high shear rates and 3D flow of the polymer melt. Moreover, modelling of the mechanical properties of the micro parts based on mathematical systems used for macro parts leads to large errors. This study proposes a new method for modelling the effect of process parameters on the dimensional accuracy and UTS (Ultimate tensile strength) of micro walls. This results in reduction of risk and cost, and optimization of the process. The “accuracy model” relates the dimensional error to four process parameters (polymer melt and mould temperature, and injection velocity and pressure), polymer characteristics (density, specific heat capacity and thermal conductivity) and a characteristic of the machine (plunger diameter). The “mechanical model” relates the part’s UTS to the same parameters as in the accuracy model. In order to develop the “accuracy model” an understanding of the effect of process parameters on dimensional accuracy and the polymers needs to be obtained. Several sets of experiments were conducted to investigate and establish this effect. Two polymers, Polyoxymethylene (POM) and Polypropylene (PP), were used to conduct the study. The results showed that the polymer melt temperature had the highest effect, followed by injection pressure, injection velocity and mould temperature. Amongst these, injection velocity had an adverse effect on dimensional accuracy. Further analysis was done to investigate whether the effect was consistent for several sets of the parameters. Results of the experiments showed that while the effect was not linear, the trends obtained earlier were correct. The same procedure was applied to investigate the effect of process parameters on the UTS of the micro walls. Polymer melt temperature had the highest level of influence, followed by injection velocity, injection pressure and mould temperature. Increase in all parameters resulted in reduction of the UTS, except for the mould temperature. Next, the two models were developed through a method called dimensional analysis. Several dimensionless expressions were developed to form a general relationship between the parameters and the quality criteria. Then, the obtained results and data were used to find the constants and the specific form of the functions. The overall models were validated by a fresh set of selected experiments using an original brass insert. The achieved trends and models were validated experimentally, using a different mould insert with a micro channel with a different dimension. While the values for the dimensional error and UTS were different, the trends obtained before were correct for the new insert. The same trend was observed with the models. Again, predictions for PP parts had better agreement with experimental data compared to those of POM. In addition, the amount of error for the steel insert was higher, due to different thermal conductivity of the insert material and surface roughness of the micro channels.

In recent decades, scientific research giving more attention to the development of bio-based polymer composites due to the extensive usage of petroleum based fillers as well as polymer matrices for the generation of polymer composites. It is a well-known fact that the petroleum derived polymer composites raise inevitable issues such as environmental pollution, waste management and depletion of petroleum resources etc. So it is important to develop fully or partially biodegradable polymer composites without compromising the mechanical, physical and thermal properties which are required for the end use applications. In this investigation, two different types of filler materials such as sisal fibres and halloysite nanotubes were used to prepare PLA polymer composites and their morphology, physical, mechanical, dynamic mechanical, thermal, water absorption and biodegradable properties were studied. This work also involves the preparation and properties of polypropylene composites reinforced with sisal fibres and halloysite nanotubes to compare the mechanical and thermal properties with PLA composites. First, surface treatment was performed for sisal fibres in order to remove the amorphous materials such as hemicellulose, lignin and pectin from the surface of the fibres which enhances the fibre-matrix interfacial strength and mechanical properties of the fibres and their polymer composites. Sisal fibres were subjected to different surface treatments such as alkali, high intensity ultrasound (HIU), and the combination of alkali and HIU and their effects on the morphology, fibre diameter, moisture absorption, mechanical and thermal properties of untreated and surface treated sisal fibres were studied. Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FE-SEM) results confirmed the removal of amorphous materials after the combined treatments of alkali and ultrasound. Moisture absorption and diameter of the sisal fibres were significantly reduced by 40 and 200% respectively after the combination of alkali and HIU treatment as compared to untreated sisal fibres. TGA results revealed that the thermal stability of sisal fibres obtained with the combination of alkali and HIU treatment significantly increased by 38.5 oC as compared to the untreated fibres. Tensile properties of single fibre showed a reduction in the tensile strength and modulus by 25% and 26% respectively as compared to the untreated sisal fibre owing to surface treatments. A reduction in the tensile properties is mainly due to the removal of amorphous materials from the surface of sisal fibres which act as binding materials for cellulose. Second, the effect of different surface treatments on the morphology, mechanical, thermal, water absorption and biodegradable properties of sisal fibres reinforced PLA (SF/PLA) composites has been investigated. For this, different ratio of untreated and surface treated sisal fibres was mixed with PLA polymer matrix by using an internal mixer. Compounded materials from the internal mixer were subjected to compression moulding to prepare the test specimens. FE-SEM analysis confirmed the good dispersion of different surface treated SF in the PLA composites. The tensile strength and modulus increased by 10 and 75.4% for 15 wt% and 30 wt% of fibre loading respectively with the combined treatment of alkali and HIU PLA composites as compared to the untreated fibre reinforced PLA composites. Young’s modulus of the composites has also been predicted by using the theoretical models which fit well to the obtained experimental values. Dynamic-mechanical analysis (DMA) revealed that the combination of alkali and HIU treated SF/PLA composites showed an increase in the storage modulus by 15% and 30% as compared to the untreated fibre composites and pure PLA respectively. TGA and DSC analysis revealed that the thermal stability and crystallinity increased significantly for the PLA composites reinforced with sisal fibres of combined treatment of alkali and HIU. Water absorption study showed a considerable reduction in the water absorption and coefficient of diffusion by 136% and 130% respectively for the combination of alkali and HIU treated SF/PLA composites as compared to untreated SF/PLA composites. The degradation of SF/PLA composites was studied by composting the samples into the soil. A significant weight loss of 17.87% could be observed for the addition of 30 wt% of untreated SF/PLA composites after soil composting for 120 days. Apart from sisal fibres, halloysite (Hal) nanotubes were also used as reinforcement fillers to study their effectiveness in improving the mechanical and thermal properties of PLA nanocomposites. Hal nanotubes were surface modified with 3-aminopropyltriethoxysilane (APTES) to enhance the surface interaction of Hal nanotubes with PLA and to achieve good dispersion of Hal nanotubes across the PLA matrix. Nitrogen adsorption-desorption, FTIR and TGA analysis results were confirmed the successful modification of Hal nanotubes surface with APTES. The different wt% of unmodified and APTES modified Hal-PLA nanocomposites were prepared by using internal mixer and compression moulding machine. The resultant Hal-PLA nanocomposites were characterized for their morphology, thermal, mechanical and dynamic-mechanical properties. Tensile strength increased to 62.6 MPa with the addition of 4 wt% of APTES modified Hal-PLA nanocomposites which is 26.5% higher than pure PLA and 15% higher than unmodified (4 wt%) Hal-PLA nanocomposites. Impact strength of 4 wt% APTES modified Hal-PLA nanocomposites increased by 20% and 40% as compared to unmodified Hal-PLA nanocomposites and the pure PLA respectively. TGA analysis revealed that the thermal stability increased significantly by 17 oC with the addition of 4 wt % of APTES modified Hal nanotubes onto PLA. Storage modulus increased by more than 10% with the addition of 4 wt% of APTES modified Hal nanotubes as compared to pure PLA. To compare the PLA composites with conventional polymer matrix composites, composites of polypropylene (PP) were prepared by reinforcing with sisal fibres and Hal nanotubes and the effect of surface treatment of sisal fibres and surface modification of Hal nanotubes on the mechanical and thermal properties of SF/PP and Hal-PP nanocomposites were studied. Tensile properties were increased for the combined treated SF/PP composites as compared to the untreated and pure PP. Tensile modulus and strength increased by more than 50% and 10% respectively as compared to the untreated SF/PP composites. TGA and DSC results revealed that the combination of alkali and HIU treatments increased the thermal stability and crystallinity by 8 oC and 8% respectively as compared to untreated SF/PP composites. DMA analysis confirmed the significant enhancement of storage modulus for the combined treated SF/PP composites by 50% as compared to pure PP. Mechanical and thermal properties were studied for unmodified and APTES modified Hal nanotubes reinforced PP nanocomposites. The investigations suggest that the mechanical properties of APTES modified Hal-PP nanocomposites were found to be superior to the unmodified Hal-PP nanocomposites. The tensile strength and modulus increased by 31 and 72% with the addition of 6 wt% of APTES modified Hal-PP nanocomposites as compared to pure PP. Impact strength also increased by 44% than pure PP with 6 wt% loading of APTES modified Hal nanotubes. Thermal analysis revealed that the thermal stability and percentage crystallinity increased by 15 oC and 22% respectively for the Hal-PP nanocomposites with surface modification by APTES. DMA analysis shows the improved storage modulus by 28% as compared to pure PP. Based on the present work, it can be said that the sisal fibres and Hal nanotubes have potential as reinforcing materials in the generation of fully bio-based polymer composites. / However, surface treatments and/or modification were playing an important role in order to tune the required mechanical and thermal properties of the polymer composites. This study also proved that in comparison to the conventional polymer matrix materials such as PP, PLA is a strong competitor with respect to its good mechanical properties and improved thermal stability apart from the fact that PLA is one of the best known biodegradable and biocompatible polymer matrices in the current market to use not only in medical application, but also in various commercial applications such as packaging, automotive and home appliances.

The successful clinical translation of non-viral gene delivery systems has yet to be achieved due to the biological and technical obstacles to preparing a safe, potent and cost-effective vector. Hyperbranched polymers have emerged as promising candidates to address gene delivery barriers owing to their relatively simple synthesis and ease of modification compared to other polymers, which makes them more feasible for scale up and manufacturing. In the first part of this thesis, we compare hyperbranched poly(amino acids) synthesised by co-polymerising histidine and lysine, with hyperbranched polylysine prepared using the well-known 'ultra-facile' thermal polycondensation route, to investigate the effects of histidine units on the structure and gene delivery applications of the resultant materials. The conditions of polymerisation were optimised to afford water-soluble hyperbranched polylysine-co-histidine of three different molar ratios with molecular masses varying from 13-30 kDa. Spectroscopic, rheological and thermal analysis indicated that the incorporation of histidine modulated the structure of hyperbranched polylysine to produce a more dendritic polymer with less flexible branches. Experiments to probe gene delivery to A549 and H1299 cells, surprisingly, indicated that the co-polymers containing histidine were not more effective in transfecting a luciferase gene than hyperbranched polylysines synthesised as established literature comparators. We attribute the variations in gene delivery efficacy to the changes induced in polymer architecture by the branching points at histidine residues, and obtain structure-function information relating histidine content with polymer Tg, pKa and ability to form stable polyplexes with plasmid DNA. These results are of significance to nanomedicine design as they indicate that addition of histidine as a co-monomer in the synthetic route to hyperbranched polymers changes not only the buffering capacity of the polymer but has significant effects on the overall structure, architecture and gene delivery efficacy. It has become known that many cationic polymers are cytotoxic and although a large number of polycations have now designed to address the toxicity problem, there is still a practical need to develop a fast and reliable method for assessing the safety of these materials. In this regard, metabolomics provides a high throughput and comprehensive method that can assess the potential toxicity at the cellular and molecular level. Therefore, in the second part of this thesis, metabolomics was applied to investigate the impact of hyperbranched polylysine, hyperbranched polylysine-co-histidine and branched polyethylenimine polyplexes, on the metabolic pathways of A459 and H1299 cell lines. The study revealed that the polyplexes downregulated metabolites associated with glycolysis and the TCA cycle, and induced oxidative stress in both cell lines. The fold changes of the metabolites indicated that the polyplexes of polyethylenimine and hyperbranched polylysine affected the metabolism much more than the polyplexes of hyperbranched polylysine-co-histidine. This was in line with transfection results, suggesting a correlation between the toxicity and transfection efficiency of these polyplexes. This part highlights the importance of metabolomics approaches not just to assess the potential toxicity of polyplexes but also to understand the molecular mechanisms underlying their action, which could help to design more efficient vectors. In the third part of this thesis, we investigated the ability of the hyperbranched polymers to condense and deliver siRNA. The results indicated that the higher molecular mass polymers achieved better siRNA delivery and gene silencing than the lower molecular mass form of the polymers and the lysine-only polymer was more efficient than the histidinylated one. These results can be attributed to the low charge (molecular mass) and stiffness of siRNA molecules in comparison with plasmid DNA, which in combination with the impact of histidine incorporation on the structure of the hyperbranched polymers can also explain the lower efficiency of histidinylated polymers. Overall, this thesis is highlighted the impacts of structural factors on the gene delivery applications of hyperbranched polymers and the importance of these factors to inform the design of new polymeric vectors. Also, metabolomics approaches were introduced to this area, not only to evaluate the safety of gene vectors but also to understand the molecular basis by which these vectors act. The data together suggest that the hyperbranched polymers prepared during thermal polycondensation of amino acids have some efficacy in preliminary gene delivery applications, and that these might be improved with future studies to be a candidate for clinical purposes.

The field of nanomedicine has progressed to a stage where a diverse set of materials are available for controlling how a drug is delivered in the body. Although these materials can be engineered to overcome many of the obstacles associated with drug delivery, the complexity of cellular trafficking mechanisms means controlling intracellular delivery remains a major challenge. The primary portal for the cellular internalisation of nanomedicines is endocytosis, which involves transport through a network of highly complex intracellular compartments undergoing a dynamic process of acidification. As a result, nanoparticle-based pH sensors offer a new perspective from which to investigate this process. In this study, ratiometric polyacrylamide pH nanosensors were utilised to probe fundamental aspects of intracellular trafficking with the view of developing biological insights to aid the rational design of nanomedicines. Nanosensors were fabricated with a dynamic range covering the entire range of the endocytic pathway (4.0 – 7.5), with sizes between 50 and 100 nm. Endocytic uptake of nanosensors was induced in four different cell types (HeLa, 3T3, MRC-5 and JAWS II) by increasing the surface charge on the nanosensor. Dynamic pH measurements were found to be highly sensitive to experimental methodology for performing ratiometric measurements, particularly image analysis. Consequently an optimised procedure for performing ratiometric measurements was developed, and subsequently validated by correlating pH measurements with intracellular location using 3D structured illumination microscopy (3D-SIM). Application of pH nanosensors in studies investigating fundamental aspects of intracellular trafficking resulted in three key findings: 1) HeLa, 3T3 and JAWS II cells process material in different ways with respect to the extent and rate of acidification in endocytic organelles, 2) surface charge does not affect the final intracellular location of polyacrylamide nanoparticles internalised by endocytosis, and 3) lipid-mediated transfection of siRNA is associated with a greater degree of lysosomal disruption compared to cationic polymer-mediated transfection, with the former observed to show increased toxicity. These findings represent biological insights, which can be utilised to provide a rational basis for tailoring the response of pH-sensitive nanomedicines to a specific cell type, tuning the physicochemical properties of a material for more efficient intracellular trafficking and optimising siRNA formulations for endo-lysosomal release.