The rapid development of polymer nanocomposites has received extensive attention over the last few decades. The ability to alter functionalities of composites, dramatically improving properties and performance at low filler content creates flexibility in designing materials for advanced applications in various industrial fields. This work focuses on nanocomposites relevant to the packaging and aerospace industries. This work evaluated the ability to homogeneously distribute nanomaterials into a polymer matrix, understand the effects on rheological properties, understand changes to microstructure and effects, and characterize properties of resulting nanocomposite. High torque melt mixing was used to disperse surface modified cellulose nanocrystals in a poly(lactic acid) (PLA) resin and graphene in a phenylethynyl terminated imide resin, PETI 298, using bulk graphite. Rheology, Raman spectroscopy, and X-Ray powder diffraction were applied for the understanding of changes to the microstructure and location of optimum loading by the determination of the percolation threshold. Thermomechanical performance was evaluated through TGA, DMA, and DSC. It was determined that graphene and short stacks of graphene could be dispersed and distributed at low loadings in PETI 298. As expected, the addition of graphitic material led to an increase in viscosity, but also caused a retardation of the cure which could be attributed to increased viscosity or quenching of free radicals. Changes to the microstructure were difficult to evaluate because of the competing chemistry occurring in the system but it could be determined that something significant occurs around 1 wt % at which the melt rheology and the microstructure behavior was different from other composites. It was further determined that the melt mixing process led to the formation of an ordered structured. Modification of the cellulose nanocrystals (m-CNC) with Cardura, glycidyl ester, provided no improvement to mechanical properties of PLA composites. However, m-CNCs were found to nucleate the crystallization of PLA. Lack of improvement to mechanical properties could be attributed to the degradation of polymer during processing.

Master of Science / Department of Chemistry / Santosh Aryal / Nanomedicine-based therapeutics have exhibited clear benefits when compared to unmodified drugs, which include improved pharmacokinetics, drug retention, targeting efficiency, and minimizes toxicity. Every year thousands of bone cancer cases are diagnosed in the United States. Moreover, development of bone metastasis occurs in over 80% to 90% of various cancers that metastasize and signals the entry of the disease into an incurable phase. Cancer in bones can cause pain, fractures, hypercalcemia, and compression of the spinal cord, due to deposits that can erode into the bone using bone-absorbing cells. Bisphosphonates are drugs that reduce the activity of bone-absorbing cells and targets overexpressed calcium. They are characterized pharmacologically to inhibit bone resorption, skeletal distribution, and renal elimination. In addition, they can target bone microenvironment and bind strongly with calcium. The goal of this thesis is to engineer targeted nanomedicine drug with the ability to spatiotemporally control therapeutics delivery to the bone. Herein we synthesized biopolymers with functional end group moieties as alendronate (a molecular member of bisphosphate), which can target overexpressed calcium ions at the vicinity of the bone lesion where bone resorption takes place. In order to achieve our goal, a ring opening polymerization of cyclic L-lactide initiated by ALE in the presence of catalytic amount of stannous octoate was conducted in an inert environment. Thus, formed polymers are characterized for their chemistry and physicochemical properties using various analytical tools. These polymers were characterized by nuclear magnetic resonance (¹H-NMR) and Fourier Transfer Infrared Spectrometer (FT-IR), which shows monomer conversion and the presence of amide and phosphate moiety. Thereafter we engineered bone-homing polymeric nanoparticles of 80nm diameter by nanoprecipitation for controlled delivery of Dox, a first line anticancer drug used in clinics. The in-vitro results show that the nanoparticles have the ability to accumulate and internalized into the bone cancer cells, deliver drugs efficiently, and are least toxic. Therefore, innovative and efficient bisphosphonate functionalized Poly-l-lactide polymers were synthesized to target bone microenvironment.

O isosorbídeo, juntamente com o ácido láctico, é considerado importante monômero para a preparação de materiais poliméricos derivados de fontes renováveis. O presente trabalho descreve a aplicação de catalisadores de alta eficiência na síntese de poliésteres derivados de fontes renováveis. Diésteres alifáticos, isosorbídeo, lactídeo, 2-etilhexanoato de estanho II (SnOct2), triflato de itérbio [Yb(OTf)3] e triflato de ítrio [Y(OTf)3], foram utilizados como reagentes para a produção dos polímeros em estudo. O catalisador de estanho, por ser o mais comum na literatura para esse tipo de sistema, foi utilizado como referência para a aplicação dos catalisadores de alta eficiência derivados de ítrio e itérbio. A estratégia inicial adotada para a obtenção da maior massa molar possível dos polímeros foi a execução de um planejamento fatorial para avaliação de como três variáveis principais, temperatura, tempo reacional e quantidade de catalisador influenciam o processo de polimerização. Uma vez determinada a direção a ser seguida no processo de polimerização, ajustes empíricos baseados em dados e observações experimentais foram feitos com a finalidade de se otimizar as condições reacionais. Os produtos obtidos foram caracterizados por cromatografia por exclusão de tamanho, ressonância magnética nuclear de 1H e 13C, espectroscopia no infravermelho, calorimetria diferencial de varredura, análise termogravimétrica e espectrometria de massas. Catalisadores de alta eficiência foram utilizados na preparação de poliésteres de alta massa molar, sintetizados a partir de lactídeo, diésteres alifáticos e diol secundário estericamente impedido, o isosorbídeo. Polímeros ramificados inéditos foram obtidos e um novo mecanismo reacional proposto, permitindo uma melhor compreensão sobre o sistema de policondensação para derivados de isosorbídeo. / The isosorbide and lactic acid are considered important monomers from renewable sources for the preparation of biodegradable materials. The present study describes the use of high performance catalysts applied in the synthesis of polyesters from renewable sources. Aliphatic diesters, isosorbide, lactide, tin(II) 2-ethylhexanoate, ytterbium triflate and yttrium triflate were used as starting materials for producing the polymers under study. The tin catalyst, being most common in the literature for this type of system, was used as reference for application of high performance catalysts derived from ytterbium and yttrium. The initial strategy adopted to obtain the reaction conditions to reach the highest molar mass of the polymers was the implementation of an experimental design in order to evaluate how the three main variables - temperature, reaction time and amount of catalyst- influence the polymerization process. Once the direction of the polymerization process was determined based on experimental observations, further empirical adjustments were made in order to optimize the reaction conditions. The products obtained were characterized by size exclusion chromatography, 1H and 13C nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis and mass spectrometry. High efficiency catalysts were used in the preparation of high molecular weight polyesters derived from lactide, aliphatic diesters and sterically hindered diol, the isosorbide. Novel branched polymers were obtained and new mechanism was suggested, allowing a better understanding of the polycondensation reaction for isosorbide derived polymers.

The need to tailor release-rate profiles from polymeric microspheres remains one of the leading challenges in controlled drug delivery. Microsphere size, which has a significant effect on drug release rate, can potentially be varied to design a controlled drug delivery system with desired release profile. In addition, drug release rate from polymeric microspheres is dependent on material properties such as polymer molecular weight. Mathematical modeling provides insight into the fundamental processes that govern the release, and once validated with experimental results, it can be used to tailor a desired controlled drug delivery system. To these ends, PLG microspheres were fabricated using the oil-in-water emulsion technique. A quantitative study that describes the size distribution of poly(lactide-coglycolide) (PLG) microspheres is presented. A fluid mechanics-based correlation that predicts the mean microsphere diameter is formulated based on the theory of emulsification in turbulent flow. The effects of microspheres’ mean diameter, polydispersity, and polymer molecular weight on therapeutic drug release rate from poly(lactide-co-glycolide) (PLG) microspheres were investigated experimentally. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. In addition, a numerical optimization technique, based on the least squares method, was developed to achieve desired therapeutic drug release profiles by combining individual microsphere populations. The fluid mechanics-based mathematical correlation that predicts microsphere mean diameter provided a close fit to the experimental results. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the microsphere size was increased. The mathematical model gave a good fit to the experimental release data. Using the numerical optimization technique, it was possible to achieve desired release profiles, in particular zero-order and pulsatile release, by combining individual microsphere populations at the appropriate proportions. Overall, this work shows that engineering polymeric microsphere populations having predetermined characteristics is an effective means to obtain desired therapeutic drug release patterns, relevant for controlled drug delivery.

The biocompatibility and the in vivo degradation of poly(L-lactide), (PLLA)- based materials has prompted much interest in the development of these materials into scaffolds for tissue engineering applications. PLLA-based polymers have been available for use in craniomaxillofacial surgery since 1991. Usually, a plate or sheet of the polymer is placed in or over a defect in the bone. Ideally the bone will use the polymer as a support to repair the defect and as the polymer degrades, the bone will continually remodel, so that the loss of mass and mechanical strength of the polymer correlates with the increase in the mass and strength of the new bone. However, this is an ideal situation, and is not always observed in practice. The aim of this work is to develop PLLA-based materials that should encourage bone growth onto the material and allow control over the rate of degradation. PLLA-co-succinic anhydride networks were synthesised and the mineralisation and degradation of these materials were evaluated in vitro. The synthesis of these networks, involved the polymerisation of 4-arm star PLLA polymers, which were coupled through their end groups with succinic anhydride. The low molecular weight star PLLA polymers were synthesised using calcium hydride and pentaerythritol as initiator and co-initiator respectively. Calcium hydride was preferred to stannous octoate in this study as there is concern over the release of tin-containing when the polymer is implanted. As only very limited studies have been directed into the polymerisation and resulting polymers formed using calcium hydride, this was a major focus of the study. The identification of hydrogen in the reaction tubes was evidence that calcium alkoxide, formed from the reaction of pentaerythritol and calcium hydride, is the actual initiating species for the ring opening polymerisation. In situ FT-Raman spectroscopy was used as a tool to monitor the reaction process and was found to be a convenient and reliable method for obtaining information about the polymerisation kinetics. Analysis of the FTRaman kinetic curves, along with analysis of products by GPC, polarimetry and NMR spectroscopy showed that the polymerisation was 'quasi-living' depending on the ratio of pentaerythritol and calcium hydride in the system. Furthermore, both the degree of transesterification and racemisation of polymers synthesised in optimised reactions were low. The PLLA-co-succinic anhydride networks were synthesised by coupling of hydroxyl-terminated PLLA star polymers with succinic anhydride (one-pot reaction) and by coupling hydroxyl-terminated PLLA stars with succinic anhydride-terminated PLLA star polymers (two-pot reaction), using a carbodiimide, EDC to mediate the esterification. The one-pot reaction produced polymers with high gel fractions and high conversion of functional groups in the gel, whereas the gel fraction and conversion of functional groups was lower in the two-pot reaction. For the networks synthesised in the one-pot reaction, the molecular weight between crosslinks was controlled by the length of the PLLA polymer arms. The networks synthesised were characterised by FTIR-ATR spectroscopy, SEM, contact angle and by swelling. The extent of mineralisation of the PLLA-co-succinic anhydride networks in simulated body fluid (SBF) after 14 days was greater than the mineral deposition on the high molecular weight PLLA reference polymer. The degradation of the networks was carried out under accelerated conditions in 0.1 M NaOH at 37 degrees Celsius. All networks degraded much more slowly than the high molecular weight linear PLLA reference sample. The rate of degradation was found to be dependent on the crystallinity of the polymer chains, with the more crystalline networks degrading at a faster rate, while the location of the degradation, surface or bulk, was controlled by the crosslink density, showing that the degradation is 'tuneable'.

This paper presents the fabrication of controlled release devices for anticancer drug paclitaxel using supercritical antisolvent method. The thermodynamic and hydrodynamic effects during supercritical antisolvent process on the particle properties obtained were investigated. Scanning electron microscopy was employed to study particle sizes and morphologies achieved. It was observed that increasing supercritical pressure improves the surface morphology of particles obtained, and increasing the flow rate of the organic solution jet reduces the particle sizes obtained. A modified Supercritical Antisolvent with Enhanced Mass transfer setup was developed to produce monodispersed nanoparticles with high recovery yield. High performance liquid chromatography was used to determine the encapsulation efficiency and in vitro release profiles of paclitaxel loaded particles obtained. The encapsulation efficiencies of particles obtained using the modified SASEM process were high and up to 83.5%, and sustained release of paclitaxel from the polymer matrix was observed over 36 days release. The thermogram properties of the particles were also analyzed using differential scanning calorimetry to determine the crystalline state of polymer and drug. / Singapore-MIT Alliance (SMA)

O isosorbídeo, juntamente com o ácido láctico, é considerado importante monômero para a preparação de materiais poliméricos derivados de fontes renováveis. O presente trabalho descreve a aplicação de catalisadores de alta eficiência na síntese de poliésteres derivados de fontes renováveis. Diésteres alifáticos, isosorbídeo, lactídeo, 2-etilhexanoato de estanho II (SnOct2), triflato de itérbio [Yb(OTf)3] e triflato de ítrio [Y(OTf)3], foram utilizados como reagentes para a produção dos polímeros em estudo. O catalisador de estanho, por ser o mais comum na literatura para esse tipo de sistema, foi utilizado como referência para a aplicação dos catalisadores de alta eficiência derivados de ítrio e itérbio. A estratégia inicial adotada para a obtenção da maior massa molar possível dos polímeros foi a execução de um planejamento fatorial para avaliação de como três variáveis principais, temperatura, tempo reacional e quantidade de catalisador influenciam o processo de polimerização. Uma vez determinada a direção a ser seguida no processo de polimerização, ajustes empíricos baseados em dados e observações experimentais foram feitos com a finalidade de se otimizar as condições reacionais. Os produtos obtidos foram caracterizados por cromatografia por exclusão de tamanho, ressonância magnética nuclear de 1H e 13C, espectroscopia no infravermelho, calorimetria diferencial de varredura, análise termogravimétrica e espectrometria de massas. Catalisadores de alta eficiência foram utilizados na preparação de poliésteres de alta massa molar, sintetizados a partir de lactídeo, diésteres alifáticos e diol secundário estericamente impedido, o isosorbídeo. Polímeros ramificados inéditos foram obtidos e um novo mecanismo reacional proposto, permitindo uma melhor compreensão sobre o sistema de policondensação para derivados de isosorbídeo. / The isosorbide and lactic acid are considered important monomers from renewable sources for the preparation of biodegradable materials. The present study describes the use of high performance catalysts applied in the synthesis of polyesters from renewable sources. Aliphatic diesters, isosorbide, lactide, tin(II) 2-ethylhexanoate, ytterbium triflate and yttrium triflate were used as starting materials for producing the polymers under study. The tin catalyst, being most common in the literature for this type of system, was used as reference for application of high performance catalysts derived from ytterbium and yttrium. The initial strategy adopted to obtain the reaction conditions to reach the highest molar mass of the polymers was the implementation of an experimental design in order to evaluate how the three main variables - temperature, reaction time and amount of catalyst- influence the polymerization process. Once the direction of the polymerization process was determined based on experimental observations, further empirical adjustments were made in order to optimize the reaction conditions. The products obtained were characterized by size exclusion chromatography, 1H and 13C nuclear magnetic resonance, infrared spectroscopy, differential scanning calorimetry, thermogravimetric analysis and mass spectrometry. High efficiency catalysts were used in the preparation of high molecular weight polyesters derived from lactide, aliphatic diesters and sterically hindered diol, the isosorbide. Novel branched polymers were obtained and new mechanism was suggested, allowing a better understanding of the polycondensation reaction for isosorbide derived polymers.

This Thesis describes the synthesis and characterisation of new Group 2, Group 3 and lanthanide amide, alkyl, halide, borohydride and alkoxide complexes, and their uses as catalysts for the living ROP and immortal ring-opening polymerisation (iROP) of rac-, L, D- and meso-lactide. <strong>Chapter One</strong> introduces cyclic esters and possible mechanistic pathways leading to polyesters by ROP. Living and immortal ROP, including their kinetic characteristics are discussed. An overview of ROP from an industrial perspective and a literature review are also given. <strong>Chapter Two</strong> describes the synthesis and characterisation of a new series of magnesium and zinc amide, alkyl, halide, borohydride and alkoxide complexes supported by a carbazole-bis(dimethyloxazoline) ligand. Their activities towards the ROP of rac-, L- and meso-lactide are presented. Detailed mechanistic studies using spectroscopic techniques are discussed and a new mechanism is proposed. <strong>Chapter Three</strong> describes the synthesis and characterisation of a new series of calcium, strontium, yttrium, lanthanum and samarium amide, alkyl, halide, borohydride and alkoxide complexes supported by a carbazole-bis(dimethyloxazoline) ligand. Their activities towards the ROP of rac-, L- and meso-lactide are presented. Detailed mechanistic studies using spectroscopic techniques are discussed. <strong>Chapter Four</strong> describes the synthesis and characterisation of a new series of magnesium, calcium, strontium, yttrium, lanthanum and samarium amide, halide and borohydride complexes supported by a chiral carbazole-bis(isopropyloxazoline) ligand. Their activities towards the ROP of rac-, L-, D- and meso-lactide are presented. <strong>Chapter Five</strong> contains experimental details and characterising data for the new complexes reported in this Thesis. <strong>CD Appendix</strong> contains .CIF files for all the new crystallographically-characterised complexes.

No description available.

Amphiphilic block copolymers consisting of poly(ethylene oxide) and poly(lactide) have great potential for formulating drug delivery systems. Our approach was to synthesize poly(ethylene oxide-b-D,L-lactide), (PEO-b-PDLLA), block copolymers with controlled molecular weights and good functionality on the poly(ethylene oxide) end for the design of potential core-shell delivery vehicles for HIV drugs. PEO-b-PDLLA block copolymer was used as a polymeric nanocarrier to encapsulate the HIV protease inhibitor, Ritonavir, within magnetite nanoparticles. Well-defined multifunctional polymeric nanoparticles with controlled sizes and size distributions were fabricated by rapid nanoprecipitation using blends of the PEO-b-PDLLA block copolymer with poly(L-lactide), (PLLA) homopolymer. Heterobifunctional PEO oligomers were directly prepared by initiating ethylene oxide with functional alcohols bearing vinylsilane, vinylether and maleimide moieties to provide appropriate end groups for conjugating targeting ligands. The polyethers with narrow molecular weight distributions were utilized as macroinitiators for the synthesis of poly(lactide) block. Heterobifunctional diblock copolymers possessing carboxylic acids were prepared from ene-thiol addition reaction of mercaptoacetic acid across the vinyl group on the PEO end, while preserving the hydroxyl functionality on the other end. Additionally, PDLLAs bearing maleimide functionality with controlled molecular weights were synthesized using maleimide functional initiator. End group modification was performed via  Michael addition using cysteamine hydrochloride to introduce an amino group over the vinyl bond. The resulting carboxylic acid functional PEO-b-PDLLA diblock copolymers, and amino functional PDLLAs are potential biocompatible polymers that can be utilized to encapsulate an array of bioactive molecules, targeting ligands. / Master of Science