Conatumumab (AMG 655) coated nanoparticles for targeted pro-apoptotic drug delivery

Colloidal nanoparticle drug delivery systems have attracted much interest for their ability to enable effective formulation and delivery of therapeutic agents. The selective delivery of these nanoparticles to the disease site can be enhanced by coating the surface of the nanoparticles with targeting moieties, such as antibodies. In this current work, we demonstrate that antibodies on the surface of the particles can also elicit key biological effects. Specifically, we demonstrate the induction of apoptosis in colorectal HCT116 cancer cells using PLGA nanoparticles coated with Conatumumab (AMG 655) death receptor 5-specific antibodies (DR5-NP). We show that DR5-NP preferentially target DR5-expressing cells and present a sufficient density of antibody paratopes to induce apoptosis via DR5, unlike free AMG 655 or non-targeted control nanoparticles. We also demonstrate that DR5-targeted nanoparticles encapsulating the cytotoxic drug camptothecin are effectively targeted to the tumour cells, thereby producing enhanced cytotoxic effects through simultaneous drug delivery and apoptosis induction. These results demonstrate that antibodies on nanoparticulate surfaces can be exploited for dual modes of action to enhance the therapeutic utility of the modality. (C) 2011 Elsevier Ltd. All rights reserved.

NO-loaded Zn2+-exchanged zeolite materials: A potential bifunctional anti-bacterial strategy

Nitric oxide (NO) is important for the regulation of a number of diverse biological processes, including vascular tone, neurotransmission, inflammatory cell responsiveness, defence against invading pathogens and wound healing. Transition metal exchanged zeolites are nanoporous materials with high-capacity storage properties for gases such as NO. The NO stores are liberated upon contact with aqueous environments, thereby making them ideal candidates for use in biological and clinical settings. Here, we demonstrate the NO release capacity and powerful bactericidal properties of a novel NO-storing Zn2+-exchanged zeolite material at a 50 wt.% composition in a polytetrafluoroethylene polymer. Further to our published data showing the anti-thrombotic effects of a similar NO-loaded zeolite, this study demonstrates the antibacterial properties of NO-releasing zeolites against clinically relevant strains of bacteria, namely Gram-negative Pseudomonas aeruginosa and Gram-positive methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Clostridium difficile. Thus our study highlights the potential of NO-loaded zeolites as biocompatible medical device coatings with anti-infective properties. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Application of citrate-stabilized gold-coated ferric oxide composite nanoparticles for biological separations

Gold-coated magnetic nanoparticles were synthesized with size ranging from 15 to 40 nm using sodium citrates as the reducing agent. Oxidized magnetites (Fe3O4) fabricated by co-precipitation of Fe2+ and Fe3+ in strong alkaline solution were used as magnetic cores. The structures of gold (Au) shell and magnetic core (Au–Fe) were studied by transmission electron microscopy (TEM) image and energy dispersive spectroscopy (EDS) spectrum. Results from high-resolution X-ray diffraction (HR XRD) show that the Au–Fe oxide nanoparticles have a face-centered cubic shape with the crystalline faces of {1 1 1}. The Au-coated magnetic nanoparticles exhibited a surface plasmon resonance peak at 528 nm. The nanoparticles are well dispersed in distilled water. A 3000 G permanent magnet was successfully used for the separation of the functionalized nanoparticles. Magnetic properties of the nanoparticles were determined by magnetic force microscope (MFM) in nanometric resolution and vibrating sample magnetometer (VSM). Magnetic separation of biological molecules using Au-coated magnetic oxide composite nanoparticles was examined after attachment of protein immunoglobulin G (IgG) through electrostatic interactions. Using this method, separation was achieved with a maximum yield of 35% at an IgG concentration of 400 ng/ml.

Performance and wear of coated carbide drill in machining of carbon fibre reinforced composite/titanium stack

In this research we investigate the performance of drilling process in carbon fibre reinforced composite (CFC) material, titanium alloy and the hybrid stack of these two materials, using coated carbide drill bit. We study the effect of the process parameters such as the feed rate and speed on the induced forces and torques, also on the wear of drill and surface roughness of the holes. In the composite material the percentage of surface damage in both drilling CFC on its own and drilling in stack form is estimated. Also, the effect of worn drill on the surface damage is identified. In the titanium, the burr formation in stack and non-stack form is investigated. The wear of the drill results in increased forces and torques required for drilling. This increases the surface delaminations substantially at the entrance in drilling of CFC. However, the surface roughness of the holes reduces with the wear of the drill in CFC drilling. Also, the surface delamination and surface roughness of the holes in the CFC whilst drilled in hybrid form reduces significantly. This is despite the increase of the forces and torques required in drilling CFC in stack form. Copyright © 2012 Inderscience Enterprises Ltd.

Comparative study of tool life and hole quality in drilling of CFRP/titanium stack using coated carbide drill

The use of hybrid materials including carbon fiber reinforced plastics (CFRPs) and lightweight metals such as titanium are increasing particularly in aerospace applications. Multi-material stacks require a number of holes for the assembly purposes. In this research, drilling trials have been carried out in CFRP, Ti-6Al-4V and CFRP/Ti-6Al-4V stack workpieces using AlTiN coated tungsten carbide drill bit. The effects of process parameters have been investigated. The thrust force, torque, burr formation, delamination, surface roughness and tool wear have been analyzed at various processing condition. The experimental results have shown that the thrust force, torque, burr formation and the average surface roughness increase with the increased feed rate and decrease with the increased cutting speed in drilling of Ti-6Al-4V. In drilling CFRP, delamination and the average surface roughness has similar tendency with the cutting parameters however thrust force and torque rises with the increased cutting speed. The results showed that after making 15 holes in CFRP/Ti-6Al-4V stack, measured thrust forces were increased by 20% in CFRP and by 45% in Ti-6Al-4V. Delamination was found to be much smaller in drilling of CFRP in stack from compared to drilling single CFRP. Tool life was significantly shortened in drilling of stack due to the combination of the wear mechanisms.

Adsorption Study using Optimised 3D Organised Mesoporous Silica Coated with Fe and Al Oxides for Specific As(III) and As(V) Removal from Contaminated Synthetic Groundwater

This work presents the possibility of optimising 3D Organised Mesoporous Silica (OMS) coated with both iron and aluminium oxides for the optimal removal of As(III) and As(V) from synthetic contaminated water. The materials developed were fully characterised and were tested for removing arsenic in batch experiments. The effect of total Al to Fe oxides coating on the selective removal of As(III) and As(V) was studied. It was shown that 8% metal coating was the optimal configuration for the coated OMS materials in removing arsenic. The effect of arsenic initial concentration and pH, kinetics and diffusion mechanisms was studied, modelled and discussed. It was shown that the advantage of an organised material over an un-structured sorbent was very limited in terms of kinetic and diffusion under the experimental conditions. It was shown that physisorption was the main adsorption process involved in As removal by the coated OMS. Maximum adsorption capacity of 55 mg As(V).g-1 was noticed at pH 5 for material coated with 8% Al oxides while 35 mg As(V).g-1 was removed at pH 4 for equivalent material coated with Fe oxides.

Photocatalytic degradation of eleven microcystin analogues and nodularin by TiO2 coated glass microspheres

Microcystins and nodularin are toxic cyanobacterial secondary metabolites produced by cyanobacteria that pose a threat to human health in drinking water. Conventional water treatment methods often fail to remove these toxins. Advanced oxidation processes such as TiO2 photocatalysis have been shown to effectively degrade these compounds. A particular issue that has limited the widespread application of TiO2 photocatalysis for water treatment has been the separation of the nanoparticulate power from the treated water. A novel catalyst format, TiO2 coated hollow glass spheres (Photospheres™), is far more easily separated from treated water due to its buoyancy. This paper reports the photocatalytic degradation of eleven microcystin variants and nodularin in water using Photospheres™. It was found that the Photospheres™ successfully decomposed all compounds in 5 minutes or less. This was found to be comparable to the rate of degradation observed using a Degussa P25 material, which has been previously reported to be the most efficient TiO2 for photocatalytic degradation of microcystins in water. Furthermore, it was observed that the degree of initial catalyst adsorption of the cyanotoxins depended on the amino acid in the variable positions of the microcystin molecule. The fastest degradation (2 minutes) was observed for the hydrophobic variants (microcystin-LY, -LW, -LF). Suitability of UV-LEDs as an alternative low energy light source was also evaluated.

Fibre laser joining of highly dissimilar materials: Commercially pure Ti and PET hybrid joint for medical device applications

Laser transmission joining (LTJ) is growing in importance, and has the potential to become a niche technique for the fabrication of hybrid plastic-metal joints for medical device applications. The possibility of directly joining plastics to metals by LTJ has been demonstrated by a number of recent studies. However, a reliable and quantitative method for defining the contact area between the plastic and metal, facilitating calculation of the mechanical shear stress of the hybrid joints, is still lacking. A new method, based on image analysis using ImageJ, is proposed here to quantify the contact area at the joint interface. The effect of discolouration on the mechanical performance of the hybrid joints is also reported for the first time. Biocompatible polyethylene terephthalate (PET) and commercially pure titanium (Ti) were selected as materials for laser joining using a 200 W CW fibre laser system. The effect of laser power, scanning speed and stand-off distance between the nozzle tip and top surface of the plastic were studied and analysed by Taguchi L9 orthogonal array and ANOVA respectively. The surface morphology, structure and elemental composition on the PET and Ti surfaces after shearing/peeling apart were characterized by SEM, EDX, XRD and XPS.

Magnetic impurities in nanostructured materials

Os resultados apresentados aqui foram alcançados no âmbito do programa de doutoramento intitulado “Impurezas Magnéticas em Materiais Nanoestruturados”. O objectivo do estudo foi a síntese e caracterização de óxido contendo impurezas magnéticas. Durante este trabalho, sínteses de sol-gel não-aquoso têm sido desenvolvidos para a síntese de óxidos dopados com metais de transição (ZnO e ZrO2). A dopagem uniforme é particularmente importante no estudo de semicondutores magnéticos diluídos (DMSs) e o ponto principal deste estudo foi verificar o estado de oxidação e a estrutura local do dopante e para excluir a existência de uma fase secundária como a origem do ferromagnetismo. Para alargar o âmbito da investigação e explorar plenamente o conceito de "impurezas magnéticas em materiais nanoestruturados" estudamos as propriedades de nanopartículas magnéticas dispersas em uma matriz de óxido. As nanopartículas (ferrita de cobalto) foram depositadas como um filme e cobertas com um óxido metálico semicondutor ou dielétrico (ZnO, TiO2). Estes hetero-sistemas podem ser considerados como a dispersão de impurezas magnéticas em um óxido. As caracterizações exigidas por estes nanomateriais têm sido conduzidas na Universidade de Aveiro e Universidade de Montpellier, devido ao equipamento complementar.

Novel materials based on chitosan, its derivatives and cellulose fibres

O presente trabalho tem como principal objectivo o desenvolvimento de novos materiais baseados em quitosano, seus derivados e celulose, na forma de nanofibras ou de papel. Em primeiro lugar procedeu-se à purificação das amostras comerciais de quitosano e à sua caracterização exaustiva em termos morfológicos e físicoquímicos. Devido a valores contraditórios encontrados na literatura relativamente à energia de superfície do quitosano, e tendo em conta a sua utilização como precursor de modificações químicas e a sua aplicação em misturas com outros materiais, realizou-se também um estudo sistemático da determinação da energia de superfície do quitosano, da quitina e seus respectivos homólogos monoméricos, por medição de ângulos de contacto Em todas as amostras comerciais destes polímeros identificaram-se impurezas não polares que estão associadas a erros na determinação da componente polar da energia de superfície. Após a remoção destas impurezas, o valor da energia total de superfície (gs), e em particular da sua componente polar, aumentou consideravelmente. Depois de purificadas e caracterizadas, algumas das amostras de quitosano foram então usadas na preparação de filmes nanocompósitos, nomeadamente dois quitosanos com diferentes graus de polimerização, correspondentes derivados solúveis em água (cloreto de N-(3-(N,N,N-trimetilamónio)-2- hidroxipropilo) de quitosano) e nanofibras de celulose como reforço (celulose nanofibrilada (NFC) e celulose bacteriana (BC). Estes filmes transparentes foram preparados através de um processo simples e com conotação ‘verde’ pela dispersão homogénea de diferentes teores de NFC (até 60%) e BC (até 40%) nas soluções de quitosano (1.5% w/v) seguida da evaporação do solvente. Os filmes obtidos foram depois caracterizados por diversas técnicas, tais como SEM, AFM, difracção de raio-X, TGA, DMA, ensaios de tracção e espectroscopia no visível. Estes filmes são altamente transparentes e apresentam melhores propriedades mecânicas e maior estabilidade térmica do que os correspondentes filmes sem reforço. Outra abordagem deste trabalho envolveu o revestimento de folhas de papel de E. globulus com quitosano e dois derivados, um derivado fluorescente e um derivado solúvel em água, numa máquina de revestimentos (‘máquina de colagem’) à escala piloto. Este estudo envolveu inicialmente a deposição de 1 a 5 camadas do derivado de quitosano fluorescente sobre as folhas de papel de forma a estudar a sua distribuição nas folhas em termos de espalhamento e penetração, através de medições de reflectância e luminescência. Os resultados mostraram que, por um lado, a distribuição do quitosano na superfície era homogénea e que, por outro lado, a sua penetração através dos poros do papel cessou após três deposições. Depois da terceira camada verificou-se a formação de um filme contínuo de quitosano sobre a superfície do papel. Estes resultados mostram que este derivado de quitosano fluorescente pode ser utilizado como marcador na optimização e compreensão de mecanismos de deposição de quitosano em papel e outros substratos. Depois de conhecida a distribuição do quitosano nas folhas de papel, estudou-se o efeito do revestimento de quitosano e do seu derivado solúvel em água nas propriedades finais do papel. As propriedades morfológicas, mecânicas, superficiais, ópticas, assim como a permeabilidade ao ar e ao vapor de água, a aptidão à impressão e o envelhecimento do papel, foram exaustivamente avaliadas. De uma forma geral, os revestimentos com quitosano e com o seu derivado solúvel em água tiveram um impacto positivo nas propriedades finais do papel, que se mostrou ser dependente do número de camadas depositadas. Os resultados também mostraram que os papéis revestidos com o derivado solúvel em água apresentaram melhores propriedades ópticas, aptidão à impressão e melhores resultados em relação ao envelhecimento do que os papéis revestidos com quitosano. Assim, o uso de derivados de quitosano solúveis em água em processos de revestimento de papel representa uma estratégia bastante interessante e sustentável para o desenvolvimento de novos materiais funcionais ou na melhoria das propriedades finais dos papéis. Por fim, tendo como objectivo valorizar os resíduos e fracções menos nobres da quitina e do quitosano provenientes da indústria transformadora, estes polímeros foram convertidos em polióis viscosos através de uma reacção simples de oxipropilação. Este processo tem também conotação "verde" uma vez que não requer solvente, não origina subprodutos e não exige nenhuma operação específica (separação, purificação, etc) para isolar o produto da reacção. As amostras de quitina e quitosano foram pré-activadas com KOH e depois modificadas com um excesso de óxido de propileno (PO) num reactor apropriado. Em todos os casos, o produto da reacção foi um líquido viscoso composto por quitina ou quitosano oxipropilados e homopolímero de PO. Estas duas fracções foram separadas e caracterizadas.

Development of polymeric materials to inhibit bacterial quorum sensing

Bacterial infections are an increasing problem for human health. In fact, an increasing number of infections are caused by bacteria that are resistant to most antibiotics and their combinations. Therefore, the scientific community is currently searching for new solutions to fight bacteria and infectious diseases, without promoting antimicrobial resistance. One of the most promising strategies is the disruption or attenuation of bacterial Quorum Sensing (QS), a refined system that bacteria use to communicate. In a QS event, bacteria produce and release specific small chemicals, signal molecules - autoinducers (AIs) - into the environment. At the same time that bacterial population grows, the concentration of AIs in the bacterial environment increases. When a threshold concentration of AIs is reached, bacterial cells respond to it by altering their gene expression profile. AIs regulate gene expression as a function of cell population density. Phenotypes mediated by QS (QSphenotypes) include virulence factors, toxin production, antibiotic resistance and biofilm formation. In this work, two polymeric materials (linear polymers and molecularly imprinted nanoparticles) were developed and their ability to attenuate QS was evaluated. Both types of polymers should to be able to adsorb bacterial signal molecules, limiting their availability in the extracellular environment, with expected disruption of QS. Linear polymers were composed by one of two monomers (itaconic acid and methacrylic acid), which are known to possess strong interactions with the bacterial signal molecules. Molecularly imprinted polymer nanoparticles (MIP NPs) are particles with recognition capabilities for the analyte of interest. This ability is attained by including the target analyte at the synthesis stage. Vibrio fischeri and Aeromonas hydrophila were used as model species for the study. Both the linear polymers and MIP NPs, tested free in solutions and coated to surfaces, showed ability to disrupt QS by decreasing bioluminescence of V. fischeri and biofilm formation of A. hydrophila. No significant effect on bacterial growth was detected. The cytotoxicity of the two types of polymers to a fibroblast-like cell line (Vero cells) was also tested in order to evaluate their safety. The results showed that both the linear polymers and MIP NPs were not cytotoxic in the testing conditions. In conclusion, the results reported in this thesis, show that the polymers developed are a promising strategy to disrupt QS and reduce bacterial infection and resistance. In addition, due to their low toxicity, solubility and easy integration by surface coating, the polymers have potential for applications in scenarios where bacterial infection is a problem: medicine, pharmaceutical, food industry and in agriculture or aquaculture.

STANDARDIZATION OF PROCESS PARAMETERS FOR READY TO EAT FISH PRODUCTS IN INDIGENOUS POLYMER COATED TIN FREE STEEL CANS

In the present work, Indigenous polymer coated Tin Free Steel cans were analyzed fortheir suitability for thermal processing and storage of fish and fish products following standard methods. The raw materials used for the development of ready to eat thermally processed fish products were found to be of fresh condition. The values for various biochemical and microbiological parameters of the raw materials were well within the limits. Based on the analysis of commercial sterility, instrumental colour, texture, WB-shear force and sensory parameters, squid masala processed to F0 value of 8 min with a total process time of 38.5 min and cook value of 92 min was chosen as the optimum for squid masala in tin free steel cans while shrimp curry processed to F0 7 min with total process time of 44.0 min and cook value of 91.1 min was found to be ideal and was selected for storage study. Squid masala and shrimp curry thermally processed in indigenous polymer coated TFS cans were found to be acceptable even after one year of storage at room temperaturebased on the analysis of various sensory and biochemical parameters. Analysis of the Commission Internationale d’ Eclirage L*, a* and b* color values showed that the duration of exposure to heat treatment influenced the color parameters: the lightness (L*) and yellowness (b*)decreased, and the redness (a*) significantly increased with the increase in processing time or reduction in processing temperature.Instrumental analysis of texture showed that hardness-1 & 2 decreased with reduction in retort temperature while cohesiveness value did not show any appreciable change with decrease in temperature of processing. Other texture profile parameters like gumminess, springiness and chewiness decreased significantly with increase of processing time. W-B shear force values of mackerel meat processed at 130 °C were significantly higher than those processed at 121.1 and 115 °C. HTST processing of mackerel in brine helped in reducing the process time and improving the quality.The study also indicated that indigenous polymer coated TFS cans with easy openends can be a viable alternative to the conventional tin and aluminium cans. The industry can utilize these cans for processing ready to eat fish and shell fish products for both domestic and export markets. This will help in reviving the canning industry in India.

Investigations on Dezincification of Brass and Epoxy Coated Brass

Brasses are widely used as constructional materials in marine environment due to their anticorrosive,antifouling and mechanical properties.However, its resistance to corrosion and fouling may vary according to local marine environmental condition and the seasons.The dezincification of brass is one of the forms of selective corrosion which has attracted the attention of researchers for the last two decades.Many of the dezincification mechanistic studies have been performed in noncomplex media and hence their conclusions cannot be extended to esturine water,which is of great significance since brass is extensively used in marine environment.Inhibited α brasses are largely immune to dezincication and the effect of tin and arsenic addition to α/beta brasses is not so reliable in controlling the dezincification. There have been many cases of dezincification in duplex brasses in both freshwater and seawater.Though there is some protection methods such as inhibitors,electro deposition and electro polymerization,there is no reliable method of inhibiting the dezincification of two-phase brass.Organic coatings are effectively used for the protection metals due to their capacity to act a physical barrieer between the metal surface and corrosive environment.Hence,pure epoxy coating is selected for this as it has antocorrosiion effect on brass.The dezincification behaviour of brass of the present study has been highlighted in terms of corrosion rate,weight gain/loss,corrosion current and polarization resistence,open circuit potential,dezincification factor. The marine fouling as biomass on brass was assessed and presented in this thesis, The physicochemical properties of estuarine water were correlated with corrosion behaviour of brass.The deterioration of the brass subjected to the effect of estuarine water was also investigated as a measure of loss in mechanical properties such as tensile strength,yield strength,percntage elongation and percentage reduction in area.To validate dezincification data,visual observation,spot analysis,surface morphology before and after removal of corrosion products and corrosion product analysis were performed.The dezincification behavior of epoxy coated brass of the present study has beenhighlighted in terms of corrosion rate ,weight gain/loss,corrosion current and polarization resistance,open circuit potential.dezincification factor.The marine fouling as biomass on epoxy coated brass subjeted to the effect of estuarine water was also investigated as ameasure of loss in mechanical properties such as tensile strength,percentage elongation and percentage reduction in area.The results of dezincification behavior of brass and epoxy coated brass in Cochin estuary water has been presented and discussed.Attempt has been made to correlate the dezincification behavior of brass with epoxy coated brass.

Aerogel-coated metal nanoparticle colloids as novel entities for the synthesis of defined supported metal catalysts

Nanometer metal particles of tailored size (3-5 nm) and composition prepared via inverse microemulsion were encapsulated by ultrathin coatings (<2.5 nm) of inorganic porous aerogels covered with surface -OH groups. These composite materials formed metastable colloids in solvent(s), and the organic surfactant molecules were subsequently removed without leading to aggregation (the ethanolic colloid solution was shown to be stable against flocculation for at least weeks). We demonstrate that the totally inorganic-based composite colloids, after the removal of surfactant, can be anchored to conventional solid supports (gamma-alumina, carbons) upon mixing. Application of a high temperature resulted in the formation of strong covalent linkages between the colloids and the support because of the condensation of surface groups at the interface. Detailed characterizations (X-ray diffraction (XRD), pore analysis, transmission electron microscopy (TEM), CO chemisorption) and catalytic testing (butane combustion) showed that there was no significant metal aggregation from the fine metal particles individually coated with porous aerogel oxide. Most of these metal sites on the coated nanoparticles with and without support are fully accessible by small molecules hence giving extremely active metal catalysts. Thus, the product and technology described may be suitable to synthesize these precursor entities of defined metal sizes (as inks) for wash coat/impregnation applications in catalysis. The advantages of developing inorganic nanocomposite chemical precursors are also discussed.