The pursuit of optimizing soft contact lens performance has been extensive, given that approximately over 140 million contact lens wearers globally seek the convenience and visual acuity they offer. However, a persistent challenge is the prevalence of ocular dryness and discomfort experienced by almost half of these wearers, particularly towards the end of the day. The occurrence of these symptoms is primarily attributed to diminished compatibility between the contact lens and the ocular surface leading to contact lens discontinuation. A promising method to improve overall contact lens properties is to incorporate novel monomers with unique functionalities during the initial manufacturing stage. Monomers bearing ionic functional groups have been extensively explored to improve bulk and surface properties of biomaterials. The incorporation of cationic and zwitterionic monomers in the fabrication of hydrogel materials has shown to have anti-fouling and anti-bacterial properties and improved surface wetting. In this work, a series of novel materials using cationic and zwitterionic monomers were prepared and their impact on bulk and surface properties of contact lens materials were assessed. Furthermore, the impact of a novel hydrophilic silicone-based monomer bearing zwitterionic phosphocholine was investigated for water-based extraction, physiochemical and structural stability in candidate contact lens materials. In Chapter 2, a library of eleven positively charged (cationic) and electrically neutral with both positive and negative charges (zwitterionic) functional methacrylate ester monomers was produced through the reaction of 2-(dimethylamino) ethyl methacrylate (DMAEMA) with different alkyl halides. The Menshutkin reaction was carried out with a high level of success, resulting in moderate to high yields of the desired monomers. The monomers were purified and characterized using analytical techniques, including 1H-NMR (proton nuclear magnetic resonance), 13C-NMR (carbon-13 nuclear magnetic resonance), LCMS (liquid chromatography-mass spectrometry), and XRD (X-ray diffraction). Six monomers were chosen based on controlled end group hydrophilicity and chain length to investigate the relationship between chemical structure and overall performance in hydrogel and silicone hydrogel systems. In Chapters 3 and 4, model hydrogel and silicone hydrogel systems via UV free-radical polymerization at increasing input concentrations (10 and 20 wt%) were manufactured using the monomers and HEMA (hydrogel) or HEMA + SIGMA (silicone hydrogel). The novel materials demonstrated an increase in bulk equilibrium water content, reduced contact angle and nonspecific lysozyme and albumin adsorption, while maintaining optical transparency at higher than 90%. In vitro studies demonstrated the ionically charged hydrogel materials did not show any toxicity to human corneal epithelial cells. In Chapter 5, a super hydrophilic silicone-based SIGMAPC monomer was synthesized using the siloxane functional monomer (SIGMA) as the main building block. The introduction of the novel hydrophilic SIGMAPC monomer led to significant improvements in the silicone materials. The hydrogels showed increased water content and reduced water contact angles, indicating their superior hydrophilicity. Moreover, the rate of dehydration was decreased, and the nonspecific deposition of lysozyme and albumin was minimized. Importantly, the optical transparency of the hydrogel silicone remained above 90%. Based on these findings, it can be concluded that the siloxane-based monomer bearing a zwitterionic phosphocholine has great potential for applications in contact lenses, given its desirable properties and biocompatibility. Furthermore, in Chapter 6, 31P-NMR and weight extraction analysis showed model contact lens materials made with SIGMAPC were effectively extracted in aqueous media at elevated temperature. Candidate materials showed good dimensional and optical stability pre- and post-thermal sterilization and over 6-month storage period. / Thesis / Doctor of Philosophy (PhD)

This thesis investigates the effect of hydrophilic polymers as novel solid couplants in ultrasonic inspection. These polymers can absorb large quantities of water, thus become soft and flexible, and also adapt themselves very well to applications. In this study, experiments were carried out by preparing three different types of polymer membranes namely [Poly(HEMA), Poly(HEMA-co-GMA), Poly(HEMA-NN&amp / #8242 / -dH2O)] with different thicknesses and monomer contents. Swelling ratios were determined in deionized water using 9mm diameter samples, cut from each polymer. Ultrasonic velocity and sound attenuation measurements were performed with pulse-echo and immersion techniques. These results were analyzed and compared with water, typical plastics and rubbers. In order to evaluate the coupling performance of hydrophilic polymers, weights of 50g, 200g, 500g and 1 kg were used as loading conditions to change the pressure applied to the transducer. Results obtained with this study showed that hydrophilic polymers offer low attenuation at high frequencies and couple effectively while eliminating the risk of test piece contamination. The study also revealed that velocities of polymers decrease by increasing the water content. This research can be used as a guideline for an alternative choice of couplant while testing water sensitive materials in safety critical structures or where the test piece is avoided from contamination and also can be used for rough surfaces.

Content removed due to copyright restrictions: E I-Sherbiny, I.M., Lins, R.l , Abdel-Bary, E.M., Harding, D.R.K. Preparation, characterization, swelling and in vitro drug release behaviour of poly[Nacryloylglycine- chitosan] interpolymeric pH and thermally-responsive hydrogels. Eur. Polym. J. 41 (2005) 2584. E I-Sherbiny, I.M., Abdel-Bary, E.M., Harding, D. R.K. Preparation and swelling study of a pH-dependent interpolymeric hydrogel based on chitosan for controlled drug release. Inl. J. Polym. Mater. 55 (2006) 789. El-Sherbiny, I.M., Abdel-Bary, E.M., Harding, D. R. K. Swelling characteristics and in-vitro drug release study with pH and thermo-sensitive hydro gels based on modified chitosan. J. Appl. Polym. Sci. 102 (2006) 977. Abdelaal, M.Y., Abdel-Razik, E . A , Abdel-Bary, E.M., El-Sherbiny, I.M. Study on chitosan-poly(vinyl alcohol) interpolymeric pH-responsive hydrogel films for controlled drug delivery. J. Appl. Polym. Sci. (2006) in press. El-Sherbiny, I. M., Abdel-Bary, E.M., Harding, D. R. K. In-vitro investigation of new biodegradable pH-responsive hydrogel beads for oral delivery of protein drugs in the small intestine. New Zealand Institute of Chemistry Conference (NZIC), (2006) Rotorua, New Zealand, 2-6 December. / Controlled drug release enhances the safety, efficacy and reliability of drug therapy. Regulation of the drug release rate results in a reduction in the frequency of drug administration and should encourage patients to comply with dosing instructions. Hydrogels are crosslinked, three-dimensional hydrophilic polymers, which swell without dissolving when brought into contact with water or other biological fluids. The number of polymers suitable for the controlled release of viable therapeutics is quite limited because of inherent toxicity or lack of certain properties such as biodegradability. In this thesis, chitosan was chosen as the base polymer for the development of new hydrogels that can be tailored for use in the site-specific delivery of drugs to the gastrointestinal tract. Chitosan is a non-toxic and biodegradable polymer obtained through the alkaline deacetylation of natural chitin. The interesting characteristics of chitosan make it an ideal candidate for use in controlled drug release formulations. However, chitosan exhibits some shortcomings such as hydrophobicity and a high pH-dependency for its physical properties. Hence, it is very difficult to control drug release with chitosan itself because of the various pH values of the internal organs of the human body. This may negatively affect the human body because of drug under- or over-release. In a structured programme, some new chitosan-based hydrogels have been prepared for controlled drug release investigations by applying three main approaches to overcome the shortcomings of chitosan. The first approach was the incorporation of chitosan into interpenetrating polymer network hydrogels with either a hydrophilic polymer or with hydrophilic monomers treated to bring about in situ copolymerization in the presence of chitosan and a suitable crosslinking agent. The second approach was the chemical modification of chitosan by grafting of a suitable vinyl macromer such as poly(ethylene glycol)-diacrylate, then crosslinking this modified chitosan. The equilibrium swelling studies were carried out for the hydrogels prepared using these two approaches at 37 °C at pH 2.1 (simulated gastric fluid, SGF) and at pH 7.4 (simulated intestinal fluid, SIF). The swelling results showed a pH-responsive nature of these hydrogels. They attained higher swelling values in SGF than in SIF. 5-Fluorouracil (5-FU), an anti cancer drug, was entrapped as a model drug in all the hydrogels prepared using these two approaches. The in-vitro drug release studies were carried out at 37 °C in SGF and SIF. From the preliminary investigations of the prepared hydrogels, they may be customized and used to expand the utilization of these systems in drug delivery applications. In the third approach, chitosan was modified in such a fashion that the hydrogels produced were also pH-responsive but attained limited swelling in SGF and higher swelling in SIF. Hence, the resulting hydrogels could be tailored for utilization for intestine-targeted delivery of peptide and protein drugs with a potential protection of the drugs from the harsh acidity of the stomach. In this third approach the ionotropic gelation was used for the preparation of the hydrogels based on the modified chitosan with another natural polymer (sodium alginate) in the presence of a divalent ion. Bovine serum albumin (BSA) was entrapped as a model protein drug and the in-vitro drug release profiles were established at 37 °C in SGF and SIF. The results showed promising release profiles of BSA. However, this hydrogel study requires more effort to limit the swelling and consequently the loss of drug in the SGF, to act as an excellent candidate for intestine-specific delivery of peptide and protein drugs.

Content removed due to copyright restrictions: E I-Sherbiny, I.M., Lins, R.l , Abdel-Bary, E.M., Harding, D.R.K. Preparation, characterization, swelling and in vitro drug release behaviour of poly[Nacryloylglycine- chitosan] interpolymeric pH and thermally-responsive hydrogels. Eur. Polym. J. 41 (2005) 2584. E I-Sherbiny, I.M., Abdel-Bary, E.M., Harding, D. R.K. Preparation and swelling study of a pH-dependent interpolymeric hydrogel based on chitosan for controlled drug release. Inl. J. Polym. Mater. 55 (2006) 789. El-Sherbiny, I.M., Abdel-Bary, E.M., Harding, D. R. K. Swelling characteristics and in-vitro drug release study with pH and thermo-sensitive hydro gels based on modified chitosan. J. Appl. Polym. Sci. 102 (2006) 977. Abdelaal, M.Y., Abdel-Razik, E . A , Abdel-Bary, E.M., El-Sherbiny, I.M. Study on chitosan-poly(vinyl alcohol) interpolymeric pH-responsive hydrogel films for controlled drug delivery. J. Appl. Polym. Sci. (2006) in press. El-Sherbiny, I. M., Abdel-Bary, E.M., Harding, D. R. K. In-vitro investigation of new biodegradable pH-responsive hydrogel beads for oral delivery of protein drugs in the small intestine. New Zealand Institute of Chemistry Conference (NZIC), (2006) Rotorua, New Zealand, 2-6 December. / Controlled drug release enhances the safety, efficacy and reliability of drug therapy. Regulation of the drug release rate results in a reduction in the frequency of drug administration and should encourage patients to comply with dosing instructions. Hydrogels are crosslinked, three-dimensional hydrophilic polymers, which swell without dissolving when brought into contact with water or other biological fluids. The number of polymers suitable for the controlled release of viable therapeutics is quite limited because of inherent toxicity or lack of certain properties such as biodegradability. In this thesis, chitosan was chosen as the base polymer for the development of new hydrogels that can be tailored for use in the site-specific delivery of drugs to the gastrointestinal tract. Chitosan is a non-toxic and biodegradable polymer obtained through the alkaline deacetylation of natural chitin. The interesting characteristics of chitosan make it an ideal candidate for use in controlled drug release formulations. However, chitosan exhibits some shortcomings such as hydrophobicity and a high pH-dependency for its physical properties. Hence, it is very difficult to control drug release with chitosan itself because of the various pH values of the internal organs of the human body. This may negatively affect the human body because of drug under- or over-release. In a structured programme, some new chitosan-based hydrogels have been prepared for controlled drug release investigations by applying three main approaches to overcome the shortcomings of chitosan. The first approach was the incorporation of chitosan into interpenetrating polymer network hydrogels with either a hydrophilic polymer or with hydrophilic monomers treated to bring about in situ copolymerization in the presence of chitosan and a suitable crosslinking agent. The second approach was the chemical modification of chitosan by grafting of a suitable vinyl macromer such as poly(ethylene glycol)-diacrylate, then crosslinking this modified chitosan. The equilibrium swelling studies were carried out for the hydrogels prepared using these two approaches at 37 °C at pH 2.1 (simulated gastric fluid, SGF) and at pH 7.4 (simulated intestinal fluid, SIF). The swelling results showed a pH-responsive nature of these hydrogels. They attained higher swelling values in SGF than in SIF. 5-Fluorouracil (5-FU), an anti cancer drug, was entrapped as a model drug in all the hydrogels prepared using these two approaches. The in-vitro drug release studies were carried out at 37 °C in SGF and SIF. From the preliminary investigations of the prepared hydrogels, they may be customized and used to expand the utilization of these systems in drug delivery applications. In the third approach, chitosan was modified in such a fashion that the hydrogels produced were also pH-responsive but attained limited swelling in SGF and higher swelling in SIF. Hence, the resulting hydrogels could be tailored for utilization for intestine-targeted delivery of peptide and protein drugs with a potential protection of the drugs from the harsh acidity of the stomach. In this third approach the ionotropic gelation was used for the preparation of the hydrogels based on the modified chitosan with another natural polymer (sodium alginate) in the presence of a divalent ion. Bovine serum albumin (BSA) was entrapped as a model protein drug and the in-vitro drug release profiles were established at 37 °C in SGF and SIF. The results showed promising release profiles of BSA. However, this hydrogel study requires more effort to limit the swelling and consequently the loss of drug in the SGF, to act as an excellent candidate for intestine-specific delivery of peptide and protein drugs.

Therapeutics based on siRNA represent a promising hope for the treatment of many congenital and acquired disorders. This method is based on posttranscriptional silencing of pathological gene or set of genes (RNAi process), which are responsible for the actual cause of the disease. Access is therefore based on the assumption of treatment options for the disease at the point of origin of the defect intervention at the molecular level, which is different from the conventional, so-called symptomatic therapy, which focuses only on the treatment or suppression of symptoms. Despite rapidly increasing understanding of gene function and cause a number of genetic diseases, the expansion of siRNA therapeutics limited the development of efficient and safe transport systems (vectors). In order to ensure efficient transport of siRNA in vivo conditions, the vectors must sufficiently reduce the size of the siRNA, protect it against degradation during transport, and release in the cytoplasm of the target cell. For this purpose they were developed sophisticated transport systems based on viral and non-viral origin. This diploma thesis is focused on the preparation of new transport systems, siRNA-based synthetic hydrophilic polymers, such as non-viral vectors. For in vitro testing the effectiveness during transport of siRNA...

Surface modification techniques have played important roles in various aspects of modern technology. They have been employed to improve substrates by altering surface physicochemical properties. An ideal surface modifying technique would be a method that is applicable to any kind of materials prepared from a wide range of polymers and that can occur under mild reaction conditions. The work in this thesis has utilized four main concepts: I) the development of a ‘grafting-from’ technique by covalently growing polymer grafts from particle surfaces, II) the presence of steric and electrosteric forces due to long-range repulsive interactions between particles, III) a combined surface grafting and layer-by-layer approach to create polyelectrolyte multilayers (PEMs) on particle surfaces to fabricate strong and functional materials, and IV) the roles of hydrophilic polymer grafts and substrate geometry on surface degradation. A non-destructive surface grafting technique was developed and applied to polylactide (PLA) particle surfaces. Their successful modification was verified by observed changes to the surface chemistry, morphology and topography of the particles. To quantify the aggregation behavior of grafted and non-grafted particles, force interaction measurements were performed using colloidal probe atomic force microscopy (AFM). Long-range repulsive interactions were observed when symmetric systems, i.e., hydrophilic polymer grafts on two interacting surfaces, and asymmetric system were applied. Electrosteric forces were observed when the symmetric substrates interacted at pH 7.4. When PEMs were alternately assembled on the surface of poly(L-lactide) (PLLA) particles, the grafted surfaces played a dominated role in altering the surface chemistry and morphology of the particles. Three-dimensional scaffolds of surface grafted particle coated with PEMs demonstrated high mechanical performance that agreed well with the mechanical performance of cancellous bone. Nanomaterials were used to functionalize the scaffolds and further influence their physicochemical properties. For example, when magnetic nanoparticles were used to functionalize the scaffolds, a high electrical conductivity was imparted, which is important for bone tissue regeneration. Furthermore, the stability of the surface grafted particles was evaluated in phosphate buffered saline (PBS) solution. The nature of the hydrophilic polymer grafts and the geometry of the PLLA substrates played central roles in altering the surface properties of films and particles. After 10 days of PBS immersion, larger alterations in the surface morphology were observed on the film compared with microparticles grafted with poly(acrylic acid) (PAA). In contrast to the PAA-grafted substrates, the morphology of poly(acrylamide) (PAAm)-grafted substrates was not affected by PBS immersion. Additionally, PAAm-grafted microparticulate substrates encountered surface degradation more rapidly than PAAm-grafted film substrates. / <p>QC 20151002</p>

Ces travaux de recherche s'inscrivent dans le développement de nouveaux catalyseurs pour les piles à combustible de type PEMFC. L'objectif est d'améliorer le transfert de charges et de matières au sein des électrodes afin d'améliorer la durabilité des matériaux. Nous avons développé des catalyseurs qui permettent la transposition de la phénoménologie du point triple à l'échelle moléculaire. Le greffage de polymères conducteurs protoniques à la surface de nanoparticules de platine a été réalisé afin d'obtenir des complexes catalytiques nano-composites, comportant le catalyseur au platine, un conducteur protonique et un conducteur électronique. L'ensemble des matériaux issus de cette première étape ont été caractérisé en demi-cellule électrochimique afin de déterminer les catalyseurs les plus actifs et les plus sélectifs. Les matériaux les plus prometteurs ont enfin été testés en mono-cellule PEMFC de 5 cm² et 25 cm² afin de déterminer d'une part les performances in situ et d'autre part la durabilité des matériaux. Les électrodes nano-composites, formulées sans Nafion®, ont des caractéristiques équivalentes aux systèmes commerciaux. En effet, elles fournissent une densité de puissance maximale de 1 W.cm-2 et une durabilité de 20 µV.h-1 sur 300 h. Ces électrodes formulées sans composé fluoré permettent le recyclage du platine par pyrolyse. / This research work is within the scope of new catalysts for PEM fuel cells. The objective is to decrease the platinum amount in the electrode and to promote mass and electronic transfers, in order to improve the durability of the systems. We developed catalysts that enable the implementation of the phenomenology of the triple phase boundary at the molecular scale. The fieldwork concerns the grafting of proton conducting polymers (PSS) on the platinum nanoparticles surface in order to obtain nanocomposite catalysts. All synthetized materials are characterized in electrochemical half-cell, in order to determine the most active and the most selective catalyst. Then, the best catalytic complexes are tested in PEMFC 5 cm² and 25 cm² single-cell to determine in situ performance and materials durability. The properties of the nanocomposites electrodes formulated without Nafion®, are equivalent to commercial systems. Indeed, they provide a maximum power density of 1 W.cm-2 and a durability of 20 µV.h-1 during 300 h. These electrodes formulated without fluorinated compound allow platinum recycling by pyrolysis.