Thermo-oxidative stabilization of poly(lactic acid) with antioxidant intercalated layered double hydroxides

Two antioxidant modified layered double hydroxides (AO-LDHs) were successfully prepared by theintercalation of 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid (IrganoxCOOH) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) in the layered structure of LDH. It was foundthat by anchoring the phenolic moieties to the LDH layers the antioxidant power is retained in the caseof Trolox, and even amplified in the case of IrganoxCOOH. A small amount of the two AO-LDHs wasincorporated into poly(lactic acid), PLA, by solution mixing and melt extrusion. The thermo-oxidativestability of the composites was compared with that of the neat PLA and PLA containing free AOs. SECanalysis indicates that, after a controlled period of ageing, both the AO-LDHs protect the PLA fromchain scission. The oxidation induction time (OIT, DSC) at 230 °C shows also the beneficial effects ofthe presence of the functional filler in the polymer matrix. Further, results from a preliminary migrationtest suggest that the AO species have a low tendency to migrate away from the AO-LDHs embedded inthe polymer matrix thus keeping the AO protected inside the nanofiller layers thereby remaining activefor a longer time.

Coordination networks of Cu2+ ions with 1,3-bis[2-(4-pyridyl)ethyl]benzene : strong structure-directing role of the counter ion (nitrate, acetate and sulphate), leading to clusters, sheets and chains

Date of Acceptance: 16/10/2015

Coordination networks of Cu2+ ions with 1,3-bis[2-(4-pyridyl)ethyl]benzene : strong structure-directing role of the counter ion (nitrate, acetate and sulphate), leading to clusters, sheets and chains

Date of Acceptance: 16/10/2015

Evaluation of a gelatin modified poly(ɛ-caprolactone) film as a scaffold for lung disease

Lung transplantation is a necessary step for the patients with the end-stage of chronic obstructive pulmonary disease. The use of artificial lungs is a promising alternative to natural lung transplantation which is complicated and is restricted by low organ donations. For successful lung engineering, it is important to choose the correct combination of specific biological cells and a synthetic carrier polymer. The focus of this study was to investigate the interactions of human lung epithelial cell line NCl-H292 that is involved in lung tissue development with the biodegradable poly(ϵ-caprolactone) before and after its chemical modification to evaluate potential for use in artificial lung formation. Also, the effect of polymer chemical modification on its mechanical and surface properties has been investigated. The poly(ϵ-caprolactone) surface was modified using aminolysis followed by immobilization of gelatine. The unmodified and modified polymer surfaces were characterized for roughness, tensile strength, and NCl-H292 metabolic cell activity. The results showed for the first time the possibility for NCI-H292 cells to adhere on this polymeric material. The Resazurin assay showed that the metabolic activity at 24 hours post seeding of 80% in the presence of the unmodified and greater than 100% in the presence of the modified polymer was observed. The roughness of the poly(ϵ-caprolactone) increased from 4 nm to 26 nm and the film strength increased from 0.01 kN to 0.045 kN when the material was chemically modified. The results obtained to date show potential for using modified poly(ϵ-caprolactone) as a scaffold for lung tissue engineering.

MEDIUM-CHAIN-LENGTH POLY(3-HYDROXYALKANOATE) NANOPARTICLE SUSPENSIONS

The main goal of this thesis was to prepare medium-chain-length poly-3-hydroxyalkanoate (mcl-PHA) nanoparticle suspensions at high solids content (≥ 10 % w/v). A two-stage emulsification-solvent evaporation process was employed to produce poly-3-hydroxydecanoate (PHD) suspensions. The formulation and processing conditions including ultrasonication time and amplitude, selection of solvent, and selection of surfactants and their concentrations were investigated to make concentrated suspensions (10 and 30 % (w/v)) of PHD with particles less than 300 nm. Among the ionic surfactants tested to stabilize the suspension, the anionic, sodium dodecyl sulphate (SDS), and the cationic, dodecyltrimethylammonium bromide (DTAB) surfactants produced the smallest particle sizes (~100 nm). However, more stabilized nanoparticles were obtained when the ionic surfactant, SDS, was combined with any of the non-ionic surfactants tested, with polyoxyethylene octyl phenyl ether (Triton X-100) or polyoxyethylene (20) sorbitan monooleate (Tween 80) resulting in a slight increase in zeta potential over 30 days while the zeta potential with other non-ionic surfactants decreased. Mcl-PHA containing 11 and 18 % of carboxyl groups was synthesized via free radical addition reaction of 11-mercaptoundecanoic acid to the pendant double bonds of unsaturated poly-3-hydroxynonanoate (PHNU). Colloidal suspensions prepared by ultrasonication needed a surfactant to maintain stability, even at 0.4 % solids of mcl-PHA containing 11 % carboxylation (PHNC-1) unlike the stable suspensions prepared without surfactants by the titration method. Similar particle sizes (155.6 ± 8.4 to 163.4 ± 11.3 nm) and polydispersity indices (0.42 ± 0.03 to 0.49 ± 0.04) were obtained when several non-ionic surfactants were tested to minimize particle agglomeration, with the smallest particles obtained with Triton X-100. When Triton X-100 was combined with a variety of ionic surfactants, smaller nanoparticles (97.1 ± 1.1 to 121.7 ± 5.7 nm) with a narrower particle size distribution (0.21 ± 0.001 to 0.25 ± 0.003) were produced. The SDS and Triton X-100 combination was chosen to evaluate other mcl-PHAs at 10 % (w/v) solids content. Slightly smaller nanoparticles were formed with carboxylated mcl-PHAs compared to mcl-PHAs having aliphatic pendant side chains. Mcl-PHA consisting of 18 % carboxylation (PHNC-2) formed a much smaller nanoparticles and higher zeta potential.

Development of radiotracers for nuclear imaging of poly(ADP-ribose) polymerase-1 and the translocator protein in glioblastoma.

Glioblastoma (GBM) is a highly aggressive and fatal brain cancer that is associated with a number of diagnostic, therapeutic, and treatment monitoring challenges. At the time of writing, inhibition of a protein called poly (ADP-ribose) polymerase-1 (PARP-1) in combination with chemotherapy was being investigated as a novel approach for the treatment of these tumours. However, human studies have encountered toxicity problems due to sub-optimal PARP-1 inhibitor and chemotherapeutic dosing regiments. Nuclear imaging of PARP-1 could help to address these issues and provide additional insight into potential PARP-1 inhibitor resistance mechanisms. Furthermore, nuclear imaging of the translocator protein (TSPO) could be used to improve GBM diagnosis, pre-surgical planning, and treatment monitoring as TSPO is overexpressed by GBM lesions in good contrast to surrounding brain tissue. To date, relatively few nuclear imaging radiotracers have been discovered for PARP-1. On the other hand, numerous tracers exist for TSPO many of which have been investigated in humans. However, these TSPO radiotracers suffer from either poor pharmacokinetic properties or high sensitivity to human TSPO polymorphism that can affect their binding to TSPO. Bearing in mind the above and the high attrition rates associated with advancement of radiotracers to the clinic, there is a need for novel radiotracers that can be used to image PARP-1 and TSPO. This thesis reports the pre-clinical discovery programme that led to the identification of two potent PARP-1 inhibitors, 4 and 17, that were successfully radiolabelled to generate the potential SPECT and PET imaging agents [123I]-4 and [18F]-17 respectively. Evaluation of these radiotracers in mice bearing subcutaneous human GBM xenografts using ex vivo biodistribution techniques revealed that the agents were retained in tumour tissue due to specific PARP-1 binding. This thesis also describes the pre-clinical in vivo evaluation of [18F]-AB5186, which is a novel radiotracer discovered previously within the research group with potential for PET imaging of TSPO. Using ex vivo autoradiography and PET imaging the agent was revealed to accumulate in intracranial human GBM tumour xenografts in good contrast to surrounding brain tissue, which was due to specific binding to TSPO. The in vivo data for all three radiolabelled compounds warrants further pre-clinical investigations with potential for clinical advancement in mind.

Electrical characterization of the rectifying contact between aluminium and electrodeposited poly(3-methylthiophene)

A detailed investigation both of the DC and of the AC electrical properties of the Schottky barrier formed between aluminium and electrodeposited poly(3-methylthiophene) is reported. The devices show rectification ratios up to 2 x 10(4) which can be increased further after post-metal annealing. The reverse characteristics of the devices follow predictions based on the image-force lowering of the Schottky barrier, from which the doping density can be estimated, As the forward voltage increases, the device current is limited by the bulk resistance of the polymer with some evidence for injection limitation at the gold counter-electrode at high bias. In the bulk-limited regime, the device current is thermally activated near room temperature with an activation energy in the range 0.2-0.3 eV. Below about 150 K the device current is almost independent of temperature. Capacitance-voltage plots obtained at frequencies well below the device relaxation frequency indicate the presence of two distinct acceptor states, A set of shallow acceptor states are active in forward bias and are believed to determine the bulk conductivity of the polymer. A set of deeper accepters are active only for very small forward voltages and for all reverse voltages, namely when band banding causes the Fermi energy to cross these states. The density of these deeper states is approximately an order of magnitude greater than that of the shallow states. Evidence is presented also for the influence of fabrication conditions on the formation of an insulating interfacial layer at the rectifying interface. The presence of such a layer leads to inversion at the polymer surface and a modification of the I-V characteristics.

Electrical characterization of the rectifying contact between aluminium and electrodeposited poly(3-methylthiophene)

A detailed investigation both of the DC and of the AC electrical properties of the Schottky barrier formed between aluminium and electrodeposited poly(3-methylthiophene) is reported. The devices show rectification ratios up to 2 x 10(4) which can be increased further after post-metal annealing. The reverse characteristics of the devices follow predictions based on the image-force lowering of the Schottky barrier, from which the doping density can be estimated, As the forward voltage increases, the device current is limited by the bulk resistance of the polymer with some evidence for injection limitation at the gold counter-electrode at high bias. In the bulk-limited regime, the device current is thermally activated near room temperature with an activation energy in the range 0.2-0.3 eV. Below about 150 K the device current is almost independent of temperature. Capacitance-voltage plots obtained at frequencies well below the device relaxation frequency indicate the presence of two distinct acceptor states, A set of shallow acceptor states are active in forward bias and are believed to determine the bulk conductivity of the polymer. A set of deeper accepters are active only for very small forward voltages and for all reverse voltages, namely when band banding causes the Fermi energy to cross these states. The density of these deeper states is approximately an order of magnitude greater than that of the shallow states. Evidence is presented also for the influence of fabrication conditions on the formation of an insulating interfacial layer at the rectifying interface. The presence of such a layer leads to inversion at the polymer surface and a modification of the I-V characteristics.

Addition of biological functionality to poly(epsilon-caprolactone) films

Biodegradable polyesters such as poly(epsilon-caprolactone) (PCL) have a number of biomedical applications; however, their usage is often limited by a lack of biological functionality. In this paper, a PCL-based polymer containing pendent groups activated by 4-nitrophenyl chloroformate (NPC) and reactive toward primary amines has been cast into thin films. The reactivity of the films toward poly(l-lysine) and the cell adhesion peptide, GRGDS, was assessed, and their cell adhesive capabilities were characterized. ATR-FTIR analysis found that NPC functional groups were present on the surface of the cast film, and the synthesis, conjugation, and visualization of a fluorescent molecule on these films further demonstrated the success of this functionalization methodology. The immersion of these films into a solution of either poly(l-lysine) (PLL) or GRGDS in PBS (pH 7.4) and subsequent 3T3 fibroblast adhesion studies demonstrated significant improvement in cell adhesion and spreading over films cast from unmodified PCL. This investigation has shown that this novel NPC-containing polymer can be utilized in many applications where increased cellular adhesion is required, or the coupling of specific molecules to polymer surfaces is of interest.

Nano-capsules of amphiphilic poly (ethylene glycol)-block-poly (bisphenol A carbonate) copolymers via thermodynamic entrapment

The synthesis of amphiphilic poly(ethylene glycol)-block-poly(bisphenol A carbonate) (PEG-b-PC) block copolymer is presented here using a simple bio-chemistry coupling reaction between poly(bisphenol A carbonate) (PC) with a monomethylether poly(ethylene glycol) (mPEG-OH) block, mediated by dicyclohexylcarbodiimide/4-dimethylaminopyridine. This method inherently allows great flexibility in the choice of starting materials as well as easy product purification only requiring phase separation and water washing. Collective data from Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR) and modulated dynamic scanning calorimetry (MDSC) confirmed the successful attachment of the poly(ethylene glycol) (mPEG-OH) and poly(bisphenol A carbonate) (PC) blocks. The preparation of nano-capsules was carried out by sudden addition of water to PEG-b-PC copolymers dispersed in THF, resulting in the controlled precipitation (i.e. thermodynamic entrapment) of the copolymer. Nano-capsules as small as 85 nm ± 30 nm were produced using this simple and fast methodology. We also demonstrate that encapsulating a water-insoluble bisphenol A diglycidyl ether (DGEBA) epoxy resin is possible highlighting the potential use of these capsules as a chemical delivery system.

Molecular dynamics approach to the structural characterization and transport properties of poly(acrylonitrile)/N,N-dimethylformamide solutions

Poly(acrylonitrile) (PAN) in N,N-dimethylformamide (DMF) is a popular solution for producing large variety of polymer products. To precisely describe the behaviours of PAN and DMF in the synthesis processes, it is significant to call for more details about the structure, some thermodynamic and dynamical properties of PAN-DMF solutions. A PAN-DMF solution was simulated via molecular dynamics with an all-atom OPLS type potential in both the NPT and NVT ensembles. The simulation results were evaluated with quantum mechanical calculations (MP2/6-311 ++G(d,p) and counterpoise procedure) and were compared with available experimental results. The liquid structure was illustrated with pair correlation functions and transport and dynamics properties were calculated with the mean-square displacements MSD and the velocity autocorrelation functions. The strong H-bonds of C≡N « H-C=O, CH » O=C-H and CH2 O=C-H, with distances of 2.55 Å, 2.55 Å and 2.65 Å, respectively, were found. The largest interaction energy of - 7.157 kcal/mol between DMF molecules and PAN molecules was found at 4.9 Å center-of-mass distance. A potential profile of intermolecular interaction of DMF with PAN along the interaction distance was presented, clearly showing an increase of DMF vaporisation heat when it getting close to PAN molecules. This provided very useful information to analyse the vaporisation behaviours of DMF at the microscopic level, which is essential to comprehensively understand molecular rearrangements towards the design of synthetic processes. The impact of the presence of the PAN on the DMF solution properties were also benchmarked with pure DMF solution.

Synthesis and self-assembly behaviour of poly(Nα-Boc-l-tryptophan)-block-poly(ethylene glycol)-block-poly(Nα-Boc-l-tryptophan)

We report for the first time the use of Nα-Boc-l-tryptophan for the synthesis of amphiphilic BAB triblock copolymers for potential drug delivery applications. A library of poly(Nα-Boc-l-tryptophan)-block-poly(ethylene glycol)-block-poly(Nα-Boc-l-tryptophan) (PBoclTrp-b-PEG-b-PBoclTrp) amphiphilic copolymers were synthesized through the ring opening polymerization of Nα-Boc-l-tryptophan Nα-carboxy anhydride as initiated by diamino-terminated PEG of fixed molecular weight (Mn 3350). The influence of the hydrophobic block length over self-assembly was investigated for 4 of the BAB copolymers of molecular weights varying between Mn 5000 and Mn 17000. It was found that an increase in hydrophobic block length led to an increase in hydrodynamic size of aggregates in solution, as well as a decrease in critical micelle concentration. TEM analysis showed the formation of spherical micelles with the largest of the copolymers forming interconnected networks of spherical micelles. The influence of hydrophobic block length over the formation of secondary structure was analyzed using circular dichroism and infrared spectroscopy. Collectively we found that the presence of t-Boc protected l-tryptophan leads to the preferential formation of α-helix secondary structure through hydrogen bonding, which, in a drug delivery vehicle context, could help in controlling drug release. Also, it is believed that the use of novel Nα-Boc-l-tryptophan could improve drug stabilization in the hydrophobic core via π-π interactions between indole rings.

Medium-Chain-Length Poly (3-Hydroxyalkanoate) Nanoparticle Suspensions

Thesis (Master, Chemical Engineering) -- Queen's University, 2016-08-16 04:58:55.749