This thesis aims to investigate different infrared absorbing molecules and how their properties are affected by their incorporation into polymer nanoparticles. Metal-free phthalocyanine-H2Pc, uranyl super phthalocyanine-USPc, and europium bisphthalocyanine were studied-EuPc2; the latter two capable of IR absorption. Due to the discovery of USPc’s moisture sensitivity, only H2Pc and EuPc2 were derivatized to facilitate encapsulation in polystyrene nanoparticles through a miniemulsion polymerization. These novel phthalocyanines attained loadings of up to 41wt% and exhibit substantial broadening of absorption peaks. Furthermore, the EuPc2 loaded particles also reveal an unprecedented gain in extinction coefficient of the NIR and radical absorption peaks. The leaching behavior of the dye was also studied, as this had not been undertaken in the literature, and revealed the need for a method of polymerizing/chemically binding phthalocyanines into nanoparticles; with preliminary steps taken to realize this goal.

This thesis aims to investigate different infrared absorbing molecules and how their properties are affected by their incorporation into polymer nanoparticles. Metal-free phthalocyanine-H2Pc, uranyl super phthalocyanine-USPc, and europium bisphthalocyanine were studied-EuPc2; the latter two capable of IR absorption. Due to the discovery of USPc’s moisture sensitivity, only H2Pc and EuPc2 were derivatized to facilitate encapsulation in polystyrene nanoparticles through a miniemulsion polymerization. These novel phthalocyanines attained loadings of up to 41wt% and exhibit substantial broadening of absorption peaks. Furthermore, the EuPc2 loaded particles also reveal an unprecedented gain in extinction coefficient of the NIR and radical absorption peaks. The leaching behavior of the dye was also studied, as this had not been undertaken in the literature, and revealed the need for a method of polymerizing/chemically binding phthalocyanines into nanoparticles; with preliminary steps taken to realize this goal.

Ulm, Univ., Diss., 2008. Esterification.

Les mini ou nanoémulsions sont des systèmes fréquemment rencontrés dans différents domaines : cosmétique, pharmaceutique, biomédical… Plusieurs procédés permettent la préparation de nanoémulsions. Cependant, ils présentent tous des limitations en termes de taille des gouttelettes, d’énergie de mélange, de rapport de viscosité entre les phases dispersées et continues, de gamme de pression à appliquer… Ce travail s’intéresse au développement d’un nouveau dispositif basé sur un écoulement élongationnel pour l’élaboration de miniémulsions de monomères. La démarche a consisté d’abord à étudier l’influence des paramètres liés au procédé proprement dit puis à la formulation du système sur la taille des gouttelettes. Cette étude a permis de comprendre les mécanismes mis en jeu lors de la fragmentation des gouttes. Une analyse dimensionnelle a ensuite été développée afin de corréler les tailles obtenues aux paramètres étudiés, par l’utilisation des nombres adimensionnels appropriés. Finalement, des expériences de synthèse en miniémulsion ont été conduites pour tenter de combiner dans le même dispositif les fonctions d’émulsificateur et de réacteur de polymérisation, dans une perspective d’intensification du procédé. / Mini or nanoemulsions are widely used in different fields like cosmetic, pharmaceutic and biomedical… Different processes allow the preparation of nanoemulsions. However, they all present limitations in terms of droplet size, mixing energy, viscosity ratios, pressure ranges… This work focused on the development of a new process based on elongational flow for theelaboration of miniemulsions. The approach consisted in studying the influence of the process and formulation parameters on droplet sizes. This study allowed us to better understand the mechanisms of drop breakup. Then, a dimensional analysis was carried out in order to correlate the obtained droplet sizes to the studied parameters by the use of the appropriate dimensionless numbers. Finally, miniemulsion synthesis experiments were performed in order to try to combine, in the samedevice, both emulsification and polymerization, in the prospect of process intensification.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / CoordenaÃÃo de AperfeÃoamento de Pessoal de NÃvel Superior / O objetivo desse trabalho foi investigar a produÃÃo de mono (MG) e diglicerÃdeos (DG) a partir da hidrÃlise e/ou glicerÃlise enzimÃtica de um triglicerÃdeo (TG), utilizando-se a tÃcnica de miniemulsÃo. Utilizou-se como substrato o triglicerÃdeo do Ãcido caprÃico, a tricaprilina. Dois tipos de lipases foram utilizadas neste estudo a fim de se estudar a regioseletividade da reaÃÃo de hidrÃlise em miniemulsÃo. A lipase Rhizopus arrhizus (RAL) com regiosseletividade especÃfica sn-1,3 e a lipase Pseudomonas cepacia (PS) devido a sua ausÃncia de regioseletividade. Uma vez que hidrÃlise e glicerÃlise ocorrem na interface Ãleo-Ãgua, diferenÃas na Ãrea interfacial pela variaÃÃo da quantidade de surfactante e a influÃncia da concentraÃÃo das lipases tambÃm foram estudadas. AlÃm disso, a glicerÃlise foi estudada pela adiÃÃo de glicerol na preparaÃÃo da miniemulsÃo com o objetivo de direcionar a formaÃÃo dos produtos para uma maior quantidade de monoglicerÃdeos. Os produtos das reaÃÃes foram caracterizados e quantificados pelas tÃcnicas de H1-RMN e HPLC. Por HPLC obteve-se as quantidades totais de cada componente (MG, DG, Ãcido graxo livre e glicerol) enquanto que por RMN, pode-se calcular as quantidades individuais de cada produto formado (1-MG, 2-MG, 1,2-DG e 1,3-DG). Observando-se as concentraÃÃes dos produtos formados na hidrÃlise catalisada pela lipase PS, pÃde-se concluir que essa lipase, conhecida por sua nÃo-especificidade, catalisou a reaÃÃo preferencialmente na posiÃÃo sn-2, tendo como principais produtos 1,3-DG e 1-MG, com concentraÃÃes mÃximas de 29% e 22%, respectivamente. Por outro lado, a hidrÃlise catalisada pela lipase RAL, teve como principais produtos 1,2-DG e 2- MG, com concentraÃÃes mÃximas de 24% e 18%, respectivamente. Os resultados corroboram com a preferÃncia dessa lipase pela posiÃÃo sn-1,3. Observou-se para a glicerÃlise em miniemulsÃo catalisada pela lipase RAL, que a adiÃÃo de glicerol mudou o perfil de formaÃÃo de 1-MG e 2-MG, alcanÃando um mÃximo de 10-12% e 32-35%, respectivamente, apÃs 4h, comparado com 8 e 22-25% durante hidrÃlise. JÃ para glicerÃlise catalisada pela lipase PS, os resultados mostraram que essa lipase, que apresentou preferÃncia pela posiÃÃo sn-2 na hidrÃlise, passou a ter comportamento similar ao da lipase RAL, sn-1,3 especÃfica. / The aim of this study was to investigate the production of mono (MG) and diglycerides (DG) from the enzymatic hydrolysis and/or glycerolysis of a triglyceride (TG), using the technique of miniemulsion. As substrate, the triglyceride of the caproic acid, the tricaprylin was used. Two types of lipases were used in this study in order to examine the regioselectivity of the hydrolysis reaction in miniemulsion. The Rhizopus arrhizus lipase (RAL) known as specific sn-1,3 and the Pseudomonas cepacia (PS) known as non-specific lipase. Since hydrolysis and glycerolysis occur in the oil-water interface, differences in the interfacial area by varying the amount of surfactant concentration and the influence of the lipase were also studied. Additionally, glycerolysis was studied by adding glycerol to prepare the miniemulsion in order to increase amount of monoglycerides as products. The products were characterized and quantified by the 1H-NMR and HPLC techniques. HPLC afforded the quantification of total amount of each component (MG, DG, free fatty acid and glycerol) whereas by NMR, it was possible to calculate the amounts of each individual isomers (1-MG, 2-MG, 1,2-DG e 1,3-DG). The concentrations of the isomers formed in the lipase PS catalyzed hydrolysis showed that this lipase, known for its non-specificity, catalyzed the reaction preferentially at the sn-2 position, having as main products 1,3-DG and 1-MG, with maximum concentrations of 29% and 22%, respectively. On the other hand, hydrolysis catalyzed by lipase RAL has as main products 1,2-DG and 2-MG with maximum concentrations of 35% and 25% respectively, at 4h. The results corroborate the preference of the lipase for the sn-1,3 position. The initial addition of glycerol to the reaction catalyzed with lipase RAL did not significantly affect the reaction profiles and the formation rates of the diglycerides. However, the introduction of glycerol changes the profile of the formation of 1- and 2-monocaprylin, reaching the concentration maximum of 10-12% and 32-35% after 4h compared to 8% and 22-25% during the hydrolysis reaction, respectively. Lipase PS, an unspecific enzyme (slight preference for the sn-2-position in hydrolysis in miniemulsion) showed in presence of glycerol a behavior similar to RAL, a sn-1,3 specific lipase.

Les travaux de cette thèse présentent la synthèse par une polymérisation RAFT en miniémulsion de nanoparticules fluorescentes (NPFs) polymères à coeur BODIPY copolymérisé au styrène et à couronne hydrophile biocompatible et fonctionnalisable à base de poly(oxyde d'éthylène) et de poly(acide acrylique). Les propriétés de fluorescence de ces NPFs ont été étudiées par spectroscopie de fluorescence stationnaire et résolue en temps. L'élaboration de la synthèse de ce type de NPFs, et la mise au point d'un procédé "one-pot" sont présentés dans un premier temps. Ensuite, les propriétés spectroscopiques de ces NPFs sont étudiées, notamment l'influence de la concentration en monomères de BODIPY au coeur des NPFs pouvant mener à la formation d'agrégats peu ou pas fluorescents. Les propriétés spectroscopiques (longueur d'onde d'émission de fluorescence et rendement quantique) du coeur des NPFs ont été modulées. Cela est rendu possible en réalisant la synthèse de monomères de BODIPY portant des groupements aromatiques encombrés, ou présentant différentes fonctions polymérisables. La couronne hydrophile des NPFs a également été modifiée afin d'obtenir différentes répartitions des unités acide acrylique et oxyde d'éthylène dans les chaînes de copolymères en surface. Ces nouvelles NPFs sont également synthétisées par un procédé "one-pot". Enfin, des molécules à fonctions amine (fluorophores, protéines) ont été introduites dans la couronne hydrophile de ces diverses NPFs par une chimie de couplage peptidique sur les fonctions acides carboxyliques. Des nano-senseurs de pH ratiométriques ont ainsi pu être élaborés. / This PhD work presents the synthesis of fluorescent nanoparticles (FNP) via a RAFT miniemulsion polymerisation and the analysis of their fluorescence properties. The core of the FNPs is a copolymer of styrene and a BODIPY monomer, and the shell, which is biocompatible and functionnalisable, is made of poly(ethylene oxyde) and poly(acrylic acid). First of all, the synthesis' optimisation of those FNPs is presented, and to the development of a one-pot process. Then, the fluorescence properties of those FNPs are studied, especially the impact of the BODIPY monomer concentration on the formation of non or weakly fluorescent aggregates. In order to change the FNP's spectroscopics properties (fluorescent quantum yield and emission wavelength), novel fluorescent BODIPY monomers have been synthesized. Those monomers presents either some bulky aromatics substituants, either variable polymerisable functions. The FNPS's hydrophilic shell has also been modified to get different distributions of the acrylic acid and ethylene oxyde units in the polymer chains of the FNPs' surface. Those new FNPs are also synthesized via a one-pot process. At last, molecules bearing an amine function (fluorescent dyes, proteins) have been grafted onto the differents FNPs' shell via a peptid coupling reaction on the carboxylic acid functions. As such, some pH ratiometric nano-sensors have been developped.

L’objectif de cette thèse est de synthétiser des nanoparticules dans des microsystèmes en copolymère d’oléfine cyclique (COC), en vue du développement d’une nouvelle phase stationnaire de chromatographie présentant des performances améliorées. Dans un premier temps, la base théorique du projet est présentée. Les performances chromatographiques d’une colonne en fonction de la taille des particules qui la constituent sont présentées, en termes de résolution et d’efficacité, ainsi qu’en temps d’analyse. L’utilisation de nanoparticules s’avère optimale, mais l’état de l’art sur les différents types de colonnes et de modes de séparations en microsystèmes montre la difficulté technique de cet objectif. Les différentes voies de synthèse de nanoparticules par polymérisation radicalaire en micro et miniémulsion sont ensuite détaillées. Les essais préliminaires ont permis de définir la méthodologie d’approche : 1) la synthèse de nanoparticules par polymérisation radicalaire en miniémulsion et 2) la fonctionnalisation indispensable des supports COC. Dans un premier temps, la composition de la miniémulsion a été optimisée par plan d’expériences. La meilleure formulation permet la synthèse, après photopolymérisation, de nanoparticules monodisperses de diamètre moyen inférieur à 200 nm. Une étude d’ancrage des nanoparticules sur plaques COC est ensuite réalisée. L’optimisation du greffage d’un monomère polyéthylène glycol diacrylate (PEGDA) est réalisée par plan d’expériences. La synthèse photochimique des nanoparticules sur des surfaces COC fonctionnalisées PEGDA permet l’obtention de nanoparticules sphériques et monodisperses de taille inférieure à 200 nm répondant parfaitement au cahier des charges. Ce travail constitue une première étape dans la réalisation de phases stationnaires innovantes en chromatographie / The aim of this thesis is the synthesis of nanoparticles in cyclic olefin copolymer (COC) microchips in order to develop a new stationary phase. The bibliography review reveals the interest of this project in increasing column performance (efficiency and resolution) and reducing the analysis time. A general review on stationary phases and separation mode in microchips is presented. The synthesis of nanoparticles by radical polymerization of micro and miniemulsion is then detailed. The preliminary results helped defining the methodological approach: 1) Synthesis of nanoparticles via miniemulsion radical polymerization and 2) functionalization of COC surfaces. First, miniemulsion composition is optimized by an experimental design. The optimal miniemulsion led, after photopolymerization, to monodisperse nanoparticles with a diameter size inferior to 200 nm. The anchorage on COC surface is then investigated and shows that COC functionalization with a hydrophilic monomer is essential. Photografting of polyethylene glycol methacrylate (PEGDA) optimization is carried out by an experimental design. The UV synthesis of nanoparticles on COC surfaces functionalized by PEGDA is demonstrated. Monodisperse and spherical nanoparticles with a diameter size inferior to 200 nm are obtained. This work is considered as a first step in the development of a new stationary phase for chromatography

No description available.

Les nanogels sont de bons candidats pour la délivrance d’actifs. Ces réseaux de polymères réticulés et de taille nanométrique, sont gonflés d’eau. Ils sont donc capables d’encapsuler une protéine à l’intérieur de leurs pores et de la libérer en fonction de l’état de gonflement du réseau. Cet état peut être modulé par la densité de réticulation du réseau ou par l’application d’un stimulus externe tel que le pH, la température ou encore une biomolécule telle que le glucose. Ainsi, les nanogels sensibles au glucose se présentent comme des candidats idéaux pour administrer l’insuline de façon asservie à la glycémie. Afin de satisfaire aux critères de biocompatibilité et de biorésorption des vecteurs, nous avons choisi de développer des nanogels à base de polysaccharide, en particulier à base d’acide hyaluronique (HA). Ceux-ci sont obtenus par réticulation du HA, préalablement modifié par des fonctions réticulables telles que les méthacrylates, dans des nanogouttes d'émulsion eau-dans-huile. Des nanogels de taille et de porosité modulables ont été synthétisés grâce à un bon contrôle 1) de la modification chimique des précurseurs par des fonctions réticulables (taux de méthacrylation), 2) de l’émulsion matricielle (taille, stabilité), 3) des conditions de réticulation par photopolymérisation gouvernant le taux de conversion des méthacrylates. Ce savoir-faire a ensuite été appliqué à la synthèse de nanogels modifiés par des dérivés de l’acide phénylboronique, ligand du glucose, afin d’obtenir des matériaux dont le taux de gonflement varie en fonction de la glycémie. L’intérêt applicatif de ces objets a été évalué vis-à-vis des propriétés d’encapsulation de l’insuline, de dégradabilité enzymatique, et de biocompatibilité. / Nanogels are an attractive class of delivery systems. These soft particles, made of highly swollen polymer network, can physically entrap a drug and release it at a rate depending on its diffusion though the network. Therefore, any change in the swelling degree can trigger the release kinetics. This parameter can be tuned by modifying the density of cross-links in the gel matrix or by changing the environmental conditions such as pH, temperature or analyte such as glucose. Thus, glucose-responsive nanogels are good candidates to be used as self-regulated systems for insulin delivery. To fulfill both biocompatibility and biodegradability criteria, our attention has been focused on the design of new nanogels made of polysaccharides, in particular made of hyaluronic acid (HA), as a main constituent. HA was at first covalently modified with polymerizable methacrylate functions and confined in nanoreactors during photopolymerization using water-in-oil miniemulsions as template. Biodegradable nanogels with a well-defined size and various cross-linking degrees were thus achieved, thanks to a good control of 1) the chemical modification of HA with methacrylates (degree of methacrylation) 2) the emulsion template (size, stability), 3) the photopolymerization conditions which governed the conversion rate of the polymerization. Further modification of the polysaccharide with phenylboronic acid as a glucose-sensitive group yielded nanogels whose swelling behavior could vary as a function of glucose concentration. These systems were further studied as insulin delivery systems. Moreover, their biodegradability, stability and biocompatibility were assessed.

Thesis (PhD)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The use of co-sonication (ad-miniemulsion) polymerisation for the preparation of highly filled polymer/clay hybrid latexes is described. Laponite (Lap) content levels in the range of 10–50 wt% were effectively encapsulated in both polystyrene (PS) and polystyrene-co-butyl acrylate nanoparticles (PSBA). The latex and film morphological features of these highly filled hybrid materials were evaluated using both transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS). PS/Lap latexes exhibited mixed particle morphologies from armoured particles at low clay content (10 wt%) to encapsulated particles at high clay content (50 wt%). However, PSBA/Lap hybrid latexes exhibited predominantly crumpled particle morphologies through the clay content studied. The resultant polymer/clay nanocomposites (PCNs) of PS/Lap and PSBA/Lap exhibited either partially or fully exfoliated structures. It was found that generally these PCNs exhibited superior properties than the neat polymers except for thermal stability properties. As much as 5000% storage modulus improvement was observed for both PS/Lap and PSBA/Lap relative to the neat polymers. The Tg of PSBA/Lap showed a 14 ºC shift towards higher temperature. Rheology tests showed that the resultant PCNs exhibited solid-like viscoelastic behaviour. The encapsulation of montmorilonite clay (MMT) using the ad-miniemulsion procedure was found to be ineffective. The MMT platelets remained adhered onto the polymer particles surfaces. Ineffective encapsulation of MMT platelets was attributed to their dimensions which were either large or equal to those of the polymer particles. Despite the ineffective encapsulation, the MMT platelets were completely exfoliated within the final PCNs as shown by both SAXS and TEM. Overall, the ad-miniemulsion was found to be an effective method for the preparation of highly filled water based polymer/clay hybrid latexes. However, the clay encapsulation in polymer particles and the extent of clay exfoliation were found to be dependent on clay dimensions relative to the polymer particles, monomer/clay compatibility and clay modifier reactivity. It was found that clay dimensions and use of clay modifier that improve monomer/clay compatibility enhances encapsulation. On the other hand, the modifier reactivity influenced the extent of clay exfoliation in the final PCN, irrespective of clay encapsulation in the polymer particles. These findings were based on comparative studies conducted on the use of Lap versus MMT and non-reactive modifier versus reactive modifier during ad-miniemulsion polymerisation. / AFRIKAANSE OPSOMMING: Die gebruik van mede-sonikasie (ad-miniemulsie) polimerisasie vir die voorbereiding van die hoogsgevulde polimeer/klei hibriedlatekse word beskryf. Laponiet (Lap) vlakke in hoeveelhede van 10-50 gew% is effektief ge-inkapsuleer in beide polistireen (PS) en polistireen-ko-butielakrilaat nanopartikels (PSBA). Die morfologiese eienskappe van die latekse en films van hierdie hoogsgevulde hibried materiale is geëvalueer deur beide transmissie-elektronmikroskopie (TEM) en klein-hoek X-straal-verstrooiing (SAXS). PS/Lap latekse het gemengde partikel morfologieë getoon, bv. vanaf gepantserde partikels by lae kleihoeveelhede (10 gew%) tot ge-inkapsuleerde partikels by hoë kleihoeveelhede (50 gew%). Daarteenoor het PSBA/Lap hibriedlatekse „n oorwegend verkreukelde partikelmorfologie getoon vir die reeks kleihoeveelhede wat bestudeer is. Die gevolglike polimeer/klei nanokomposiete (PKNs) van PS/Lap en PSBA/Lap het, óf gedeeltelike, óof ten volle geëksfolieerde strukture getoon. Oor die algemeen is bevind dat hierdie PKNs beter eienskappe as die suiwer polimere getoon het, behalwe vir die termiese stabiliteit eienskappe. Verbeteringe van soveel as 5000% in die stoormodulus is waargeneem vir beide PS/Lap en PSBA/Lap met betrekking tot die suiwer polimere. Die Tg van PSBA/Lap het „n 14°C verskuiwing na „n hoër temperatuur getoon. Reologiese toetse het getoon dat die gevolglike PKNs vastestofagtige visko-elastiese gedrag getoon het. Die inkapsulering van montmorilonietklei (MMT), deur middel van die ad-miniemulsieproses, was ondoeltreffend. Die MMT plaatjies het agtergebly op die oppervlaktes van die polimeerpartikel. Oneffektiewe inkapsulering van MMT plaatjies is toegeskryf aan hul grootte, wat óf groter, óf gelyk was aan dié van die polimeerpartikels. Ten spyte van die oneffektiewe inkapsulering was al die MMT plaatjies in die finale PKNs geëksfolieer soos deur beide SAXS en TEM aangedui. Oor die algemeen is bevind dat ad-miniemulsie „n effektiewe metode is vir die voorbereiding van hoogsgevulde waterbasis polimeer/klei hibriedlatekse. Daar is egter bevind dat klei inkapsulering in polimeerpartikels asook die omvang van klei eksfoliëring, afhanklik is van die klei afmetings in verhouding tot die polimeerpartikels, monomeer/klei verenigbaarheid en die reaktiwiteit van die kleiwysiger. Daar is bevind dat die klei afmetings en die gebruik van „n kleiwysiger wat die monomeer/klei verenigbaarheid verbeter, inkapsulering bevorder. Aan die ander kant het die reaktiwiteit van die kleiwysiger die omvang van klei eksfoliëring in die finale PKNs beïnvloed, ongeag van klei inkapsulering in die polimeerpartikels. Hierdie bevindings is gebaseer op vergelykende studies van die gebruik van Lap teenoor MMT en nie-reaktiewe wysiger teenoor reaktiewe wysiger gedurende ad-miniemulsiepolimerisasie.