Les polylactides (PLA) sont une famille de polymères biodégradables et biocompatibles de la famille des polyesters aliphatiques. Lorsque le PLA est dans un milieu humide et à une température excédant le 60°C, il se dépolymérise rapidement par hydrolyse, étape préalable à la biodégradation du PLA. Le PLA est utilisé dans le domaine biomédical et dans la fabrication de nombreux produits destinés, entre autres, à l’usage alimentaire tels que des emballages, des ustensiles et de la vaisselle jetable. Cependant, quand des applications à longue durée de vie sont visées, sa dégradation peut devenir une propriété non désirable. À cet égard, le mélanger avec un autre polymère est une des alternatives les plus simples et peu coûteuses afin de limiter cette dégradation. Le polyméthacrylate de méthyle (PMMA), un polymère thermoplastique et biocompatible avec de bonnes propriétés mécaniques et thermiques, est un candidat potentiel. Ce travail de recherche, divisé en deux étapes, consiste en l’étude de l’hydrolyse du PLA puis celle des mélanges PLA/PMMA aux températures supérieures à leur température de transition vitreuse, cela en milieu neutre, en milieu alcalin et, en certains cas, en milieu acide. La première étape de ce travail comprend l’étude de l’hydrolyse du PLA en fonction de sa capacité à cristalliser ainsi que de la température et de l’acidité du milieu d’hydrolyse en phase aqueuse. Pour l’effet de composition, deux PLA commerciaux qui différaient dans leurs ratios de compositions d’énantiomères L- et D- ont été sélectionnés. Le premier de ces PLA avait la capacité de cristalliser jusqu’à un taux d’environ 40% alors que le second était complètement amorphe. L’hydrolyse a été effectuée dans l’eau distillée (pH égal à 5.3) à 60, 70 et 80 °C pour évaluer l’effet de la température. Ensuite, les PLA ont été soumis à l’hydrolyse en milieu acide (pH égal à 1) et alcalin (pH égal à 12) à une température constante de 70°C afin d’évaluer l’effet de l’acidité et l’alcalinité du milieu. L’hydrolyse a été réalisée en suivant l’évolution de la perte de masse, du pourcentage d’eau absorbée, de l’évolution de la distribution de masse molaire et finalement de la température de fusion et du changement d’enthalpie qui y est associé. Les résultats ont montré que l’hydrolyse en milieu acide et neutre procède par un mécanisme d’érosion massique (i.e. érosion dans le cœur de l’échantillon) tandis qu’en milieu alcalin, l’hydrolyse du PLA suit principalement un mécanisme d’érosion surfacique. La cinétique de l’hydrolyse a été modélisée avec succès à l’aide d’un modèle exponentiel à deux étapes qui prend en compte chaque étape du mécanisme d’érosion. Indépendamment de leur composition énantiomérique et même si tous les échantillons étaient amorphes au début des essais, ils ont cristallisé rapidement durant l’hydrolyse. Dans une deuxième étape, l’hydrolyse des mélanges PLA/PMMA a été étudiée. L’ajout du PMMA avait pour but de ralentir la progression de l’hydrolyse puisque ce matériau est un polymère d’addition insensible à l’hydrolyse. Les mélanges préparés par extrusion ont été soumis à l’hydrolyse en milieu neutre et en milieu alcalin à 80°C durant 30 et 5 jours, respectivement. Le milieu acide n’a pas été utilisé, car, dans la première étape du travail, le comportement en hydrolyse y a été trouvé similaire à celui en milieu neutre. Les résultats montrent que le PMMA n’a aucune influence sur le développement de la cristallinité durant l’hydrolyse car le PLA a cristallisé rapidement dans les deux milieux. La réduction de la masse molaire durant l’hydrolyse a causé une réduction de la température et de l’enthalpie de fusion du PLA. La présence du PMMA a fortement amélioré l’intégrité structurelle des mélanges. À cet effet, une teneur aussi faible que 5% de PMMA retardait significativement la fragmentation des échantillons par comparaison au PLA pur. Néanmoins, le PMMA n’a eu aucune influence sur la diffusion de l’eau dans la matrice polymérique. De plus, la présence du PMMA n’a joué aucun rôle sur la cinétique de l’hydrolyse du PLA lorsque le mécanisme en cause était l’érosion massique (i.e. milieu neutre). Par contre, en milieu alcalin, où le mécanisme d’érosion surfacique est prédominant, la perte de masse et la cinétique de l’hydrolyse ont été fortement ralenties par la présence du PMMA. L’enlèvement sélectif du PLA durant l’hydrolyse a laissé une structure poreuse interconnectée d’échelle nanométrique qui n’avait été observée auparavant.

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: PharmDr. Ondřej Holas, PhD. Student: Ingrid Švehlíková Title od thesis: Lyophilization of polymeric nanoparticles Lyophilization is a widely used drying method with extensive application possibilities in the drug preparation. Its importance in pharmacy is growing because it is one of the important methods of stabilizing active substances, especially proteins. A detailed understanding of the properties of the drug and the physicochemical phenomena of the individual phases of lyophilization is a basic prerequisite for the preparation of a safe, effective and stable drug. Biomedical nanoparticles as drug carriers are the type of the dosage forms in which lyophilization is also used. A series of lyophilization experiments were performed using trehalose, mannitol, dextran and xylitol as cryo and lyoprotectant. The parameters assessed were particle size, PDI, appearance and lyophilisate reconstitution. The properties of nanoparticles prepared by nanoprecipitation from PLGA polymer were evaluated. Furthermore, experiments were performed to validate the deep-freezing method as an alternative method to lyophilization for long-term storage of nanoparticles. The nanoparticles were stored in...

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: PharmDr. Ondřej Holas, PhD. Student: Daniela Širajová Title of thesis: Preparation of polymeric fluorescent nanoparticles Nanoparticles based on biodegradable polyesters are a widely used platform for targeted drug delivery and subsequent controlled release. The aim of this diploma thesis was to prepare and optimize the preparation of polymeric nanoparticles with a fluorescent dye as a model substance. The nanoprecipitation method was used to prepare the nanoparticles. Nanoparticles prepared from two types of PLGA polymers (COOH terminated and ester terminated) were evaluated and compared. The surfactant and stabilizer were used in various concentration ratios to optimize the preparation. The surfactant was sodium cholate at concentrations of 0.1%, 0.5%, 1%, 2% and 5%. The nanoparticles were stabilized with Pluronic F-127 poloxamer at concentrations of 0.1%, 0.5% and 1%. Nanoparticles were compared in terms of encapsulation efficiency, particle size and zeta potential. In a dissolution experiment, the amount of fluorescein released was evaluated and compared as a function of time (48 hours) with acid-terminated PLGA and sodium cholate at concentrations of 0.1% and 2%....

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Despite the degradability and biocompatibility of poly(α-hydroxy acids), their utility remains limited because their thermal and mechanical properties are inferior to those of commodity polyolefins, which can be attributed to the lack of side-chain functionality on the polyester backbone. Attempts to synthesize high-molecular-weight functionalized poly(α-hydroxy acids) from O-carboxyanhydrides have been hampered by scalability problems arising from the need for an external energy source such as light or electricity. Herein, an operationally simple, scalable method for synthesizing stereoregular, high-molecular-weight (>200 kDa) functionalized polyesters have been developed by means of controlled ring-opening polymerization of O-carboxyanhydrides mediated by a highly redox reactive manganese complex and a zinc-alkoxide. Mechanistic studies indicated that the ring-opening process proceeded via the Mn-mediated decarboxylation with alkoxy radical formation (Chapter 2). In addition to the polymerization, a two-step facile chemical recycling strategy for poly(α-hydroxy acids) was developed to achieve closed-loop life cycles (Chapter 3). Moreover, this synthetic strategy is not limited to preparing homopolymers and block copolymers but also to producing stereoblock and gradient copolymers (Chapter 4). In particular, the gradient copolymers exhibited better ductility and toughness than their corresponding homopolymers and block copolymers, highlighting the potential feasibility of functionalized polyesters as strong and resilient polymeric materials (Chapter 5). Next, an atom-economical, scalable method for block copolymerization of O-carboxyanhydrides and epoxides to prepare functionalized poly(ester-b-carbonates) with high molecular weights (>200 kDa) was identified, that uses a single Lewis acidic zinc complex at room temperature in the absence of pressurized CO2 (Chapter 6). Kinetic studies showed that the first stage of the process, ring-opening polymerization of the O-carboxyanhydrides, exhibited zero-order kinetics, suggesting that the polymerization rate was independent of monomer concentration, thus allowing for a sharp switch in mechanism without a tapering effect (Chapter 7). The obtained poly(ester-b-carbonates) showed better toughness than their corresponding homopolymers and outperformed some commodity polyolefins (Chapter 8). Exploring this new chemical space of poly(ester-b-carbonates) via stereosequence-controlled synthetic methods would be a critical step toward improving this promising class of functionalized sustainable polymers (Chapter 9). / Doctor of Philosophy / Poly(α-hydroxy acids) is an environmentally friendly alternative to petrochemical polyolefins due to their excellent degradability and biocompatibility. However, it is difficult to synthesize high-molecular-weight functionalized polyesters on a large scale due to the inefficient catalysts and the need for external energy, such as light and electricity. Herein, a highly reactive Mn/Zn catalytic system for controllable O-carboxyanhydrides (OCAs) polymerization has been designed. Compared with the previously reported catalytic system, this method can be used to produce low-cost, large-scale preparation of high molecular weight (>200 kDa) polyesters without the need for external energy sources (Chapter 2). In addition, our synthesized polyesters can be completely degraded under mild conditions, thereby achieving a circular economy in the polyester industry (Chapter 3). More importantly, our operationally simple synthetic method could afford polyesters with different compositions, such as homopolymers, block copolymers, stereoblock copolymers, and gradient copolymers (Chapter 4). In particular, the obtained gradient copolymer is tough and ductile that could compete with commercial polyolefins in terms of mechanical and thermal properties, such as low-density polyethylene (LDPE) (Chapter 5). Next, we developed a single Lewis acidic zinc complex to achieve the copolymerization of OCA and epoxide to synthesize poly(ester-b-carbonates), which enriches the class of degradable polymers (Chapter 6). Moreover, this copolymerization showed unique reaction kinetics that enabled the perfectly clean switching of the polymerization mechanism during chain propagation (Chapter 7). The obtained poly(ester-b-carbonates) showed better toughness than their corresponding homopolymers and outperformed some non-degradable plastics (Chapter 8). The exploration of novel degradable polymers by sequence-controlled polymerization to replace non-degradable polyolefin on the market will continue in the near future (Chapter 9).

Novel, high molecular weight poly(dimethylsiloxane) / cycloaliphatic polyester segmented copolymers were prepared and characterized. Specifically, polyesters based on dimethyl 1,4-cyclohexane dicarboxylate and 1,4-butanediol were employed. The copolymers were synthesized via a melt process using a high trans content isomer which afforded semi-crystalline morphologies. Aminopropyl terminated poly(dimethylsiloxane) oligonlers of controlled molecular weight were synthesized and then end capped with excess diester to form a diester terminated amide linked oligomer. The latter was then incorporated into the copolymer via melt transesterification step reaction segmented copolymerization. The molecular weight of the polysiloxane and chemical composition of the copolymer were systematically varied to prepare a series of segmented polyester / poly(dimethylsiloxane) copolymers. / Ph. D.

The boundary layer effect on viscosity and injection molding studies in radial and unidirectional flows were investigated for liquid crystalline (ethylene terephthalate) using Instron model 3211 capillary rheometer. Two copolyesters of PET modified with 60 and 80 mole percent parahydroxy benzoate were examined. Melt viscosities were measured as a function of temperature and wall shear rates. Mold filling characteristics were investigated by introducing different fluid pigments into the melt before injection. Molecular orientation of the molded parts was studied by measuring the shrinkage of the microtomed samples at various temperatures, injection speeds, and cavity thicknesses for these two molds. For PET/60 mole % PHB, the viscosity was found to be some function of the capillary diameter, showing a marked decrease with decreasing capillary diameter at 275 C; this possible phenomenon is not found in most polymer melts. During mold filling stage, fluid pigments indicated that these liquid crystalline melts flow and split in the core before they approach the flow front. Molecular orientation studies showed that high shrinkage across the flow direction than that measured along the flow direction. Studies also indicated that there existed a relative maximum molecular orientation away from the surface of the parts, corresponding to the shear zone. As the cavity thickness decreases or injection speed increases, this relative maximum peak moves to the surface of the molded parts. / Master of Science

Step-growth polymerization facilitates the synthesis of a wide range of industrially applicable polymers, such as polyesters and polysulfones. The choice of backbone and end group structure within these polymers drastically impacts the final material properties and processability emphasizing the necessity for thorough understanding of structure-property relationships. Seemingly simple changes, such as exchanging a monomer for its regioisomer, affects the polymers fundamental packing structure triggering a domino effect ultimately influencing the morphological, thermal, mechanical and barrier properties. In conjunction, end groups provide a means by which tunable mechanical properties and application into unique processing methods can be achieved. Synthesizing polyesters with bibenzoate based monomers generates a large range of morphologies. Linear, 4,4' bibenzoate (4,4'BB), is widely considered a mesogenic monomer due to its ability to impart a liquid crystalline (LC) morphology on semi-aromatic polyesters with linear aliphatic spacers. In this body of work, semi-aromatic polyesters using one of 4,4'BB's regioisomers, either 3,4'BB or 3,3'BB, largely resulted in amorphous or semi-crystalline polymers depending on the selection of aliphatic diol. Incorporation of the meta isomer (3,4'BB) into traditionally LC polymers, such as poly(diethylene glycol 4,4'-bibenzoate) and poly(butylene 4,4'-bibenzoate), through copolymerization afforded two polymer series with tunable LC properties. The 3,4'BB exhibited selective disruption of crystalline domains over the LC phase generating a number of polymers with LC glass morphologies. The application of 3,4'BB to a fully-aromatic polyester enabled the synthesis of a novel melt-processable homopolyester with high thermal stability, poly(p-phenylene 3,4' bibenzoate). This structure afforded a nematic LC morphology which revealed beneficial shear-thinning properties similar to industrial standards. The unique LC morphology of this homopolyester inspired further characterization of the range of achievable properties using the basic structure, poly(phenylene bibenzoate), with all the possible regioisomers. This study afforded six polymers systematically varied in chain linearity from a completely meta to a completely para backbone configuration. A range of morphologies were achieved from high Tg amorphous polymers for the meta configurations to semi-crystalline or LC in the polymers with greater linearity. End group functionalization generates influence on polymer properties while limiting the impact on beneficial properties achieved through the backbone structure and packing. Post-polymerization reactions or the addition of a monofunctional endcapper to the polymerization both achieve end group control. In this dissertation, the addition of a monofunctional diester with a sulfonate moiety to a semi-aromatic LC polyester synthesis resulted in a telechelic ionomer. The non-covalent interaction of the ionic groups will hopefully improve the compression and transverse mechanical properties of the LCP. In contrast, post-polymerization functionalization incorporated acrylate groups onto the ends of a basic polysulfones. These reactive groups provided a handle for photo-curing which enabled the 3D printing of the polysulfones using vat photopolymerization. / Doctor of Philosophy / The research within this dissertation encompasses the design of new plastics for consumer and high-performance applications. Since the emergence of synthetic plastics in the 1920’s, these materials have become a necessity in our everyday life with a range of applications in food packaging, microelectronics, architecture, medical devices, automotive, and aerospace. Benefits over metals and glass primarily result from their light weight and wide range of mechanical properties which allow a range of material properties from soft and flexible plastic grocery bags to tough car parts. Different classes of plastics (polymers) are based primarily on the chemicals used to produce the materials, for example polyesters and polysulfones. The chemical structure of these core materials drastically impacts the final properties of the polymers, which in turn influences their application space. This work focused on how subtle changes to these starting chemical structures allows us to tune the final polymer properties. Within the class of polyesters, a focus was placed on materials known as liquid crystalline (LC) polyesters. A liquid crystalline polymer can achieve a physical state between a solid and a liquid which imparts many beneficial properties on the material processing. Liquid-crystal television displays utilized these properties to provide drastically thinner TV’s with higher resolution. Alternatively, LC polyesters find applications traditionally as high-performance fibers, insulators in microelectronics, and stainless-steel replacements in medical applications. Studying the role of chemical structure on the properties of LC polyester enabled the design of materials which improve upon the current technological standards. These changes enabled the design of LC polyesters with lower processing temperatures and the use of fewer starting materials which will inevitably save energy and money during their production. In the case of polysulfones, changing the chemical structure at the end of the polymer chain facilitated the application of novel processing methods, such as 3D printing. The ability to process using this method reduces the amount of material waste during production and provides an opportunity to design novel parts with intricate structures, inaccessible through traditional means.