Due to an increased environmental awareness and thus, concerns over the use of fossil-based monomer for polymer production, there is an ongoing effort to find alternatives to non-renewable traditional monomers. This has ushered in the rapid growth in the development of bio-based materials such as green monomers and biodegradable polymers from vegetable and animal resources. Glycerol, as a renewable bio-based monomer, is an interesting candidate for sustainable polymer production. Glycerol is a renewable material that is a by-product of the transesterification of vegetable oils to biodiesel. Utilization of the excess glycerol derived from the growing biodiesel industry is important to oleochemical industries. The main objective of this thesis was to produce high molecular weight polyglycerol from glycerol and synthesize stimuli-responsive polyglycerol hydrogels. The work began with an investigation of the step-growth polymerization of glycerol to relatively high molecular weight polyglycerol using several catalysts. The catalytic reaction mechanisms were compared and the polymer products were fully analyzed. High molecular weight partially branched polyglycerol with multimodal molecular weight distributions was obtained. The polymerization of glycerol proceeded fastest with sulphuric acid as catalyst as indicated by the highest observed conversion of monomer along with the highest molecular weights. Theoretical models were used to predict the gel point and to calculate monomer functionality. High molecular weight polyglycerol was used to synthesize novel stimuli-responsive hydrogels. Real-time monitoring of step-growth polymerization of glycerol was investigated using in-line and off-line Attenuated Total Reflectance/Fourier Transform infrared (ATR-FTIR) technique.

This degree project is a part of information and communication technology supported self-care system for the diabetes, mainly in diabetes data collection and visualization. The report is organized in four main sections: investigation and internet search, literature review, application design and implementation, system test and evaluation. Existed applications and research studies has been compared and, a responsive web application is developed aiming at providing relevant functionalities and services regarding diabetes self-management.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第23924号 / 工博第5011号 / 新制||工||1782(附属図書館) / 京都大学大学院工学研究科合成・生物化学専攻 / (主査)教授 浜地 格, 教授 古川 修平, 教授 杉安 和憲 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

Orientador: Marystela Ferreira / Resumo: Neste trabalho foram desenvolvidos diferentes tipos de filmes Layer-by-Layer (LbL) sensíveis a variação de pH, temperatura, exposição a luz e presença de carboidratos, com o objetivo de criar sistemas com resposta a estímulos que podem ser aplicados na área médica e ambiental para a entrega modificada de fármacos e pesticidas. O trabalho foi dividido em três partes, sendo o primeiro focado na liberação da emodina. Foram fabricados filmes com a emodina imobilizada diretamente e outra em que o fármaco foi encapsulado nos lipossomos formados por dipalmitoil fosfatidil glicerol (DPPG) e palmitoil fosfatidil glicerol (POPG) e então intercalado com polieletrólitos. Ambos os filmes foram expostos a condições fisiológicas e liberaram a emodina por um período prolongado em função da mudança de pH e temperatura. A segunda parte do trabalho é focado na construção de filmes com um polímero baseado em espiropirano (poli(SP-R)), um composto que quando recebe luz UV é convertido para a forma aniônica merocianina (poli(MC-R)) mudando sua cor e carga superficial. O filme foi composto pelo policátion poli(alilamina hidroclorada) (PAH) formando o (PAH/poli(SP-R))n que se desprendeu do substrato pelo processo disassembly após longo tempo de exposição à luz branca. Na terceita parte do trabalho foram desenvolvidos filmes com o polímero baseado em ácido fenil borônico (PBA), que tem a capacidade de se ligar covalentemente à açucares. Foram fabricados intercalado com PVS resultando no filme (PEI/PV... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In this work, we developed some types of Layer-by-Layer (LbL) films sensible to pH and temperature changes, light exposition and carbohydrates solutions, with the aim of to create stimuli responsive system that can be applied to medical and environmental area to drug and pesticide modulated delivery. The work was divided in three parts, the first one is based on delivery emodin. One film was fabricated with emodin immobilized directly and other the drug was encapsulated on liposomes formed by dipalmitoyl phosphatidyl glycerol (DPPG) e palmitoyl phosphatidyl glycerol (POPG) and the carrier was intercalated with polyelectrolytes. Both systems were exposed to physiologic conditions and released the emodin for prolonged time in function of pH and temperature changes. On second part of this work it was focused on construction of film with spyropiran (SP) based polymer (poli(SP-R)). The UV irradiation over (poli(SP-R)) causes the conversion to anionic and purple merocyanine molecule (poli(MC-R)) changing the color and surface charge. The film were composed by poly(allylamine hydrochloride) (PAH) and poly(SP-R) forming the (PAH/poli(SP-R))n LbL film which disassemble after long time exposed to white light. On third part of work, films were developed with phenyl borônico acid (PBA) based polymer that has the capacity to bind covalently on sugars. The films were intercalated with PVS creating the coating (PEI/PVS)2(PBAp/PVS)n. It were prepared also a film with the pyranine (PYR), the ... (Complete abstract click electronic access below) / Doutor

With the emergence of novel and more effective drug therapies, increased importance is being placed upon the methods by which these drugs are being delivered to the body. In conventional drug delivery systems, there is very little control over the release of drug. The effective concentration at the target site can be achieved by intermittent administration of grossly excessive doses, which, often results in constantly, unpredictable variations in plasma concentrations, with the risk of reaching levels below or above the therapeutic range leading to marked side effects. A plethora of formulation strategies mainly based on polymeric/lipid nanoparticles, are described in literature. Even though these systems are therapeutically advantageous in comparison to conventional systems, they remain insensitive to the changing metabolic states of the body although the symptoms of most metabolic diseases follow a rhythmic pattern.A more appropriate and effective approach of managing some of these conditions lies in the chronotherapy. This approach allows for pulsed or self-regulated drug delivery which is adjusted to the staging of biological rhythms, since the onset of certain diseases exhibits strong circadian temporal dependence. In order to reach the objective of mimicking the biophysical and biochemical processes of pathological states, many innovations in material design for drug delivery systems (DDS) that are able to release the therapeutic payload-on-demand were done to release the therapeutic agent only when it is required, according to the physiological need. The development of multidisciplinary research teams has brought huge advantages in the design, fabrication and utilization of such smart systems, especially in the pharmaceutical field. Interestingly, numerous smart polymeric materials exhibit a response to a specific stimulus. A step further, the elaboration of purpose-built monomers can give rise to compounds with tunable sensitivities or multi-stimuli responsiveness. These smart polymers demonstrate an active responsiveness to environmental (or external) signals and change their physicochemical properties as designed (e.g. conformation, solubility, shape, charge or size). As far as the stimuli are concerned, they consist of physical (e.g. temperature, ultrasound, light, electricity, magnetic or mechanical stress), chemical (e.g. pH, ionic strength) and biological signals (e.g. enzymes, biomolecules). Due to the intrapersonal variabilities which may make internal stimuli hazardous, externally controlled systems rely on externally applied stimuli that are produced by stimuli-generating devices, which results in pulsed drug delivery. This type of delivery may be rapid and allows a transient release of a determined amount of drug within a short period of time immediately after a pre-determined off-release period. A novel strategy for the formation of multi-stimuli responsive materials endowed with pH, magnetic and light sensitivity was achieved. The approach relied on the incorporation of magnetic tetrahalogenoferrate(III) anions along a polymeric backbone based on poly(2-(N,N-dimethylamino) ethyl meth-acrylate) (PDMAEMA). Starting from the same PDMAEMA, quaternized pending amine groups with various halide derivatives gave rise to magnetic materials after anion metathesis. Measuring the magnetic susceptibility of these materials exhibited that the magnetic susceptibility increased as the substituted group size decreased (become smaller) which was apparently related to the steric hindrance around the ionic pendants. Additionally, a good correlation between the magnetic susceptibility and ferric content was found. Additional experimental and theoretical Raman analyses allowed the determination of the nature of the magnetic species constituting the materials. This strategy further offers the opportunity to tailor the magnetic response through partial ammonium salt formation. In order to merge the magnetic properties of ferric-based materials with another stimuli-responsive functionality, random copolymers containing DMAEMA (D) with diazobenzene (A) unit were prepared. So, three copolymers PDA were synthesized (with targeted D/A ratios 4/6 (PDA4), 6/4 (PDA6) and 8/2 (PDA8)). Meanwhile, different degrees of amine quaternization (10, 50 and 100 %) were applied, which led to the following polymeric salts PDAX/Y where X = 4, 6, 8 (referring to the percentage of the DMAEMA unit) and Y = 10, 50 and 100 (referring to the percentage of quaternized amine groups). Finally, the aforementioned materials were converted into magnetic polymers by anion exchange. As a result, magnetic responses correlated well with amount of iron oxide in these compounds and the amount of ionic pending groups along the backbone. Moreover, the remaining tertiary amines conferred pH sensitivity to the polymers whereas the diazobenzene units ensured light responsiveness through the well-established trans-to-cis isomerization.In order to functionalize these materials in the pharmaceutical field, an intelligent delivery system was prepared. Firstly, an attempt to formulate riboflavin-5’-phosphate sodium (RPS) loaded on PDA8 microspheres was made using double emulsion evaporation method. Meanwhile, prednisolone (PRD) microspheres were prepared using s/o/w emulsion technique. Subsequently, coating systems of cochineal red tablets were developed. These tablets were coated with polymer solution (using each of three types of copolymers: PDA8, PDA6, and PDA4) until the desired percentage of the coating was achieved (10, 15, and 20 % w/w). The cumulative release profiles of cochineal red tablets coated with PDA8, PDA6, and PDA4 showed a pH-sensitive release behavior. The release in the neutral media (pH ≈ 7.0) was very slow (less than 3 % after one hour). Then, after changing the pH to 1.2, an increase in the release of cochineal was observed. Furthermore, the cumulative release of cochineal red was at the highest value for the PDA8 and the lowest for PDA4 depending on the percentage of PDMAEMA moieties. Moreover, by increasing the percentage of the coating from (10, 15 to 20 % w/w), the cumulative release of cochineal decreased. Therefore, the copolymer PDAX can be used for controlling the release of drug by changing the pH value.Finally, the cochineal tablets coated with PDA6 (10 %) showed features of light sensitivity. The release of cochineal red from coated tablets was only due to the switching in the conformational trans/cis isomerization of azobenzene moieties upon irradiation, which was confirmed by comparing the release of coated tablets with uncoated tablets upon irradiation. / Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie) / info:eu-repo/semantics/nonPublished

This thesis explores responsive images for websites, i.e., content images that respond to users display size, pixel density and bandwidth. We look into responsive web design and how it is related to responsive images. Different responsive image techniques are discussed and various use cases for responsive images are explored along with technologies that are needed to implement responsive images. A testing website is built and responsive image techniques are applied one by one, tested and compared and its effect on the websites load time is measured. The process of implementing the techniques is described with code examples and images. The results indicate that responsive images can certainly have positive effect on loading time of a website. Weather or not responsive images should be implemented depends on how much image data the website has and how fast the Internet connection is. Websites with more images can certainly profit from using responsive image techniques, especially if only slower bandwidths are available.

This thesis presents an investigation of pH-responsive, redox-sensitive poly(MMA-co- MAA) and poly(EA-co-MAA) hollow particles for the repair of load-bearing soft tissues, such as articular cartilage and the intervertebral disc. Hollow particles continue to attract major interest due to their numerous potential applications. The new method for hollow particle preparation presented in this thesis does not require the use of a colloidal template and is well suited for scaling up. Hollow particles were formed using linear poly(MMA-co-MAA) and poly(EA-co-MAA) aliphatic copolymers synthesised using free-radical chain copolymerisation performed in solution. These copolymers were dissolved in dichloromethane using methanol as a cosolvent and emulsified in water. Diffusion of the methanol into the aqueous phase prompts precipitation of the copolymer at the droplet/water interface. The more hydrophobic copolymers containing less MAA showed improved morphology compared to copolymers containing more MAA. Also, poly(EA-co-MAA) hollow particles had a more spherical morphology than poly(MMA-co-MAA) hollow particles with equivalent MAA contents. This was attributed to the lower Tg of the EA structural monomer, which resulted in more flexible particle shells. Unusually, during potentiometric titration of uncrosslinked hollow particles, the pH of the system decreased with increasing neutralisation. This behaviour is thought to be due to the unfolding of copolymer chains, exposing shielded carboxyl groups. The random structure of the copolymers is believed to be necessary for this behaviour. Crosslinked particles became swollen when the pH was increased using buffers. Concentrated dispersions formed self supporting gels, due to steric confinement, at 5 wt.%. The crosslinking process was performed by functionalising with cystamine using carbodiimide chemistry. This introduced disulphide crosslinks; which could be cleaved under reducing conditions at high pH, dissolving the gels. This ability to reduce the hollow particle shells to their constituent linear copolymer chains gives potential for natural removal from the body via extraction by the renal system. pH-triggered loading and release of a hydrophilic dye using crosslinked hollow particles was demonstrated. The similarity of the particle formation process to traditional solvent evaporation also allowed the loading of a hydrophobic dye. However, these particles were not crosslinked so release following swelling could not be investigated. Cystamine-crosslinked systems suffered from degradation due to thiol-disulphide exchange at high pH (~ pH 8). Crosslinking of one system was performed using 2-amino ethyl methacrylate (AEM). This introduced covalent, vinyl intra-shell crosslinking; which did not break down at high pH. Additional AEM was also used to allow inter-particle UVcrosslinking to form doubly crosslinked (DX) hollow-particle hydrogels. These gels did not re-disperse in buffer. To our knowledge, this is the first example of a covalent hydrogel formed from pH-responsive hollow particles. The DX gels offer improved mechanical properties compared to the singly crosslinked, physical gels. Freeze-dried samples of all of the gels produced during this study showed highly porous structures when observed using SEM. The rapid diffusion of FITC-dextran through a sample of DX gel indicates that these pores were interconnected. This is beneficial as it encourages tissue ingrowth, in addition to allowing the rapid diffusion of nutrients, oxygen and cell waste in vivo.

Due to an increased environmental awareness and thus, concerns over the use of fossil-based monomer for polymer production, there is an ongoing effort to find alternatives to non-renewable traditional monomers. This has ushered in the rapid growth in the development of bio-based materials such as green monomers and biodegradable polymers from vegetable and animal resources. Glycerol, as a renewable bio-based monomer, is an interesting candidate for sustainable polymer production. Glycerol is a renewable material that is a by-product of the transesterification of vegetable oils to biodiesel. Utilization of the excess glycerol derived from the growing biodiesel industry is important to oleochemical industries. The main objective of this thesis was to produce high molecular weight polyglycerol from glycerol and synthesize stimuli-responsive polyglycerol hydrogels. The work began with an investigation of the step-growth polymerization of glycerol to relatively high molecular weight polyglycerol using several catalysts. The catalytic reaction mechanisms were compared and the polymer products were fully analyzed. High molecular weight partially branched polyglycerol with multimodal molecular weight distributions was obtained. The polymerization of glycerol proceeded fastest with sulphuric acid as catalyst as indicated by the highest observed conversion of monomer along with the highest molecular weights. Theoretical models were used to predict the gel point and to calculate monomer functionality. High molecular weight polyglycerol was used to synthesize novel stimuli-responsive hydrogels. Real-time monitoring of step-growth polymerization of glycerol was investigated using in-line and off-line Attenuated Total Reflectance/Fourier Transform infrared (ATR-FTIR) technique.

This thesis presents a study of the preparation and characterisation of microgels (MGs) and microgel-based systems which contain a high proportion of primaryamine groups. This is carried out with the aim of being used as the precursor materials for the development of an enzyme responsive system. The particle preparations discussed in this thesis begin with a particle dispersion prepared by a polymer-polymer interaction between partially oxidised dextran (Dexox) and poly(allylamine)(PA) or poly(vinylamine) (PVAM). The particle dispersions did show good tunability of properties by altering certain variables, such as extent of oxidation which resulted in the largest  -potential change with pH. However, these particles were not viable for further work as the largest swelling ratio by volume, Q value measured was only around 1.25, not sufficient for a pH responsive property swelling change (e.g. fluid-to-gel transition or drug delivery). MG particles were prepared using a non-aqueous dispersion polymerisation of Nvinylformamide (NVF), glycidylmethacrylate (GMA) and a crosslinker, 2-(Nvinylformamido)ethyl ether (NVEE). The PNVFx-GMAy-NVEEz particles were then hydrolysed to expose the primary amine groups in the resulting PVAMx-GMAy-BEVAMEz core-shell MGs. The shell, made up of GMA and NVF prevented hydrolysis taking place on the inside of the MGs, resulting in a PVAM rich shell. These hydrolysed MGs were cationic at low pH and were shown to have polyampholyte behaviour, caused by hydrolysis of some of the GMA groups. The inclusion of the NVEE crosslinker led to increased integration of the GMA and NVF into one homogenous phase in the shell and prevented hydrolytic fragmentation. The final system studied here concerns the macroscopic gel formation between the amine-rich MGs, poly(vinylamine-co-bis(ethyl vinylamine)ether) (PVAMBEVAME)and Dexox. These mixed dispersion gels were prepared and characterised. The MGs were externally crosslinked with the Dexox in order to form an elastically effective network. This was done by forming imine bonds by reaction between the primary amine groups present on the MGs and the aldehyde groups of the Dexox. These networks displayed high storage modulus (G’) and yield strains(*) of up to 140% and the G’ values for the MG-Dexox gels increased with mass ratio (MR) of Dexox to MG. The yield strains determined from rheology remained high (~125%) with increased MR. As the imine bonds formed were not reduced, they became unstable at low pH. This was exploited in order to investigate pH-triggered gel disruption of the network. This work demonstrates that new MG/aldehyde mixtures form ductile and versatile colloidal gels and our new method provides a route to increasing ductility of hydrogels containing MG particles. This research has led to the formation of amine rich MGs, as well as an injectable gel system. These materials are well placed to be developed for enzyme responsive materials in the future.

This thesis presents an investigation of cationic microgels based on poly(N-vinylformamide-co-glycidyl methacrylate) (PNVF-GMA) and poly(N-vinylformamide-co-2-(N-vinylformamido) ethyl ether) (PNVF-NVEE). They arestudied in the context of future heteroaggregated doubly crosslinked (DX) microgelsfor damaged heart tissue repair. The microgel particles were synthesised fromPNVF-GMA, which is also a water swellable microgel. The PNVF-GMA particleshad a core-shell structure in which PNVF provides the core and PGMA creates thecross-linked shell. The morphology of particles is that of a “cane-ball” like shape. There are interconnected ridges, and this unusual morphology can be controlled bythe weight fraction of GMA used during preparation. The hydrolysed PNVF-GMA(H-PNVF-GMA) particles were both positively and negatively charged. Moreover,charge patch aggregation occurred at low ionic strength. However, these microgelswere colloidally unstable after water rinsing due to shell fragmentation. PNVF microgel particles containing (N-Vinylformamido) ethyl ether (NVEE) as acrosslinking agent were also studied to avoid the fragmentation of the particles. Thismicrogel was hydrolysed in alkali conditions to provide poly(vinylamine-co-bis(ethyl vinylamine) ether) (PVAM-BEVAME), which contains primary aminegroups. It is proposed from the data presented that the content of hydrolysis was veryhigh and the particles were stable after hydrolysis owing to the stability of etherlinkage in NVEE. These microgels were able to swell upon decreasing pH. ThePVAM-BEVAME microgel with 9 mol% of BEVAME was then used to formdoubly crosslinked (DX) microgel. To form the inter-particles crosslinking, the vinylgroups were included by functionalisation using glycidyl methacrylate (GMA)monomer. The vinyl groups of neighbouring particles were linked together via freeradical reaction. The DX microgel formed under physiological temperature andshowed extensive porosity. These DX microgels had good mechanical propertiesconfirmed by high storage modulus (G’). Moreover, the precursor gels wereinjectable which is favourable for future biomaterial applications. The study providesa new family of cationic microgel that may be suitable for a future heteroaggregatedDX microgel for heart tissue repair.