<p> In part I of this dissertation, several cationic polyacrylamides were tested under different conditions for their ability to improve the retention of fines in papermaking. A dynamic drainage jar was used to simulate the turbulence encountered in the papermaking process. Several factors, including temperature, the amount and intensity of turbulence, the additive concentration and the presence of impurities were found to affect fines retention with polymers present. A polymer made by Nalco Chemicals proved to be superior to a commonly used polymer, Percol 292 for a standard fine paper pulp. It was thought that further retention improvements might be possible by tailoring the charge density and molecular weight of polyacylamide retention aides for the specific papermaking system they are intended for. Novel approaches to retention such as those employing combinations of an anionic polymer, a cationic polymer and zirconium oxychloride were thought to show promise as well.</p> <p> In part II of this dissertation several broad polyacrylamide molecular weight standards were prepared by inverse suspension and solution processes on pilot plant equipment at the McMaster Institute for Polymer Production Technology. They were characterized by laser light scattering and viscometry at McMaster, and externally by other methods. Although the polyacrylamides prepared compare favourably to currently available commercial standards when both are analysed by SEC, further analysis must be done to be certain of the molecular weight averages.</p> <p> A relationship is presented to provide for simpler and more accurate light scattering analysis in the future. This relationship relating Mw to the second Virial coefficient may be used to eliminate some uncertainty in the often scattered plots encountered when calculating molecular weights for polyacrylamides analysed by light scattering.</p> / Thesis / Master of Engineering (MEngr)

No description available.

In recent years two-phase catalysis has been established as a new field of catalyzed processes and has achieved industrial-scale importance in olefin hydroformylation. Two-phase reactions have a number of advantages, for example, ease of separation of catalyst and product, catalysts can be tailored to the particular problem, use of special properties and effects of water as a solvent, and low environmental impact. For higher olefins (* C6), the reaction suffers low activity due to low water solubility of higher olefins. Tricesium analog of TPPTS, m,m,m-trisulfonated triphenylphosphine, was synthesized and fully characterized. Two-phase olefin hydroformylation with Rh(acac)(CO)2 was investigated. The results indicated that both activity and selectivity (linear to branch aldehyde ratio) are similar to Rh/TPPTS system. The salt effect showed that increase the solution ionic strength will increase the selectivity and decrease the activity in the olefin hydroformylation with TPPTS. A new surface active phosphine, trisulfonated tris-m-(3henylpropyl)phenylphosphine, was synthesized and fully characterized. The results of biphasic olefin hydroformylation were consistent with aggregation of the ligand. The two phase 1-octene hydroformylation results showed that with only 3 methylene groups, there is no difference between the para and meta position of C3 group. A new chelating diphosphine, tetrasulfonated 2,2'-bis{di[p-(3 phenylpropyl)phenyl]phosphinomethyl}-1,1'-biphenyl,was prepared and fully characterized. Its application in two-phase hydroformylation of olefin showed enhanced activity and selectivity compared to the non-chelated phosphine analog. Finally, homogeneous asymmetric hydrogenation was carried out in the presence of a chiral surfactant in an attempt to affect asymmetric induction. The catalytic results showed that at a surfactant/Rh ratio of 25, the asymmetric hydrogenation of AACA-Me (a-Acetamidocinnamic Acid Methyl Ester) in methanol has no effect on asymmetric induction with the introduction of this chiral surfactant. / Master of Science

Wide literature precedence exists for polymers containing electrostatic interactions and polymers containing hydrogen bonding motifs, however the combination of electrostatic and hydrogen bonding interactions is not widely investigated in current literature. Polyelectrolytes containing hydrogen bonding groups are expected to exhibit properties of both classes of supramolecular interactions. A series of adenine- and thyminecontaining PDMAEMA and tert-butyl acrylate copolymers were synthesized to investigate the effect of incorporating hydrogen bonding groups into a polyelectrolyte. Incorporation of the styrenic nucleobases significantly affected the solubility of these copolymers on aqueous solutions and showed salt-triggerability with higher contents of these groups. Polyelectrolytes are capable of binding and condensing DNA through electrostatic interactions with the negatively charged phosphate groups of the DNA backbone; however a high degree of cytotoxicity is also often observed for these gene delivery systems. The high level of cytotoxicity is attributed to high degree of cationic character for the polyplexes formed with these systems according to the proton-sponge hypothesis. One method of reducing the overall cationic character for these systems is incorporation of non-electrostatic binding mechanisms such as hydrogen bonding. A series of nucleobase-containing PDMAEMA copolymers were utilized in order to investigate the effect of incorporation of these groups on the cell viability, binding efficiency, and transfection efficiency of PDMAEMA. / Master of Science

No / Of particular importance in recent years has been the development of techniques for producing nanoparticles (NPs) of poorly-water soluble drugs with dimensions less than 1000 nm for which their high surface area can lead to improvements in bioavailability. Furthermore, the small size of these particles can also enable cellular uptake, particularly for positively charged systems. Therefore, an overall objective of this part of the project was to produce nanoparticles with different levels of positive surface charge using the bottom-up method.

Poorly water soluble drugs have been manipulated to make them more soluble, increasing the bioavailability of these drugs. Several cryogenic processes allow for production of drug nanoparticles, without mechanical stress that could cause degradation. The Ultra Rapid Freezing (URF) process is a technique which improves water solubility of drugs by reducing primary drug particle size by producing amorphous solid dispersions. Heat conduction is improved, using a cryogenic material with a high thermal conductivity relative to the solution being frozen to maintain the surface temperature and heat transfer rate while the solution is being frozen. With URF technology, the freezing rate is fixed, which drives the particle formation and determines its characteristics. Supersaturation of drug in aqueous solution can allow for better absorption of the drug via the oral and pulmonary routes. Drug formulations that supersaturate the dissolution media show the possibility for increased bioavailability from an amorphous drug form. If the concentration of drug in solution is significantly increased, higher chemical potential will lead to an increase in flux across an exposed membrane, leading to higher blood levels for an amorphous drug, compared to an identical crystalline formulation. During oral delivery, supersaturated drug concentrations would also saturate PGP efflux sites in the gut lumen, increasing the drug's bioavailability. Saturated PGP sites show zero order efflux kinetics, so increasing the drug concentration in supersaturated biological fluid will increase serum drug levels. High supersaturation levels maintained for prolonged periods would have a beneficial effect on a drug's absolute bioavailability. Pulmonary administration offers therapeutic advantages over more invasive routes of administration. Limited amount of metabolizing enzymes like CYP 3A4 in lung tissue along with avoidance of first pass metabolism are advantages to pulmonary delivery. The objective of the research presented in this dissertation is to show the versatility of nanoparticulate poorly water soluble drug formulations. Due to the reduced particle size and the URF manufacturing process, a wide range of applications can be used with these nanoparticles. Oral and pulmonary administration routes can be explored using nanoparticles, but in vitro cell culture testing can show clinical benefits from this type of processing technology. / text

Thesis (PhD)--Stellenbosch University, 2008. / ENGLISH ABSTRACT: This study concerns the synthesis, properties and quantitative analysis of polydiallyldimethylammonium chloride (polyDADMAC), a water-soluble polymer used world-wide for potable water purification. The special interest in this polymer is the result of its widespread use and the current lack of adequate analytical methods for it. This is especially important for water treatment organisations. A novel gel permeation chromatography (GPC) method was developed and evaluated for polymer analysis. The scope was extended to determine the presence of unreacted monomer (DADMAC) as well as the percentage active polymer. polyDADMAC was first prepared using a known synthesis method. The product was purified and characterized by GPC and 13C-NMR spectroscopy. New and conclusive evidence of the existence of a five-member pyrrolidine ring system was obtained. A proposed mechanism of polymerization was determined. The activity of the synthesized polyDADMAC was evaluated and it was found to perform effectively as a coagulant. The physical and chemical properties of polyDADMAC were then studied under simulated water treatment conditions. The polymer reaction with chlorine revealed the formation of trihalogenated methane compounds (THMs). Gas chromatography–mass spectrometry (GC–MS) was used to conclusively identify the formation of chloroform. The polymer stability under different conditions of heat exposure, UV radiation and pH variations was studied. GPC results indicated that polyDADMAC is a very stable polymer and undergoes structural change only when subjected to extremes of pH, temperature and UV conditions. Results of a short study on microbial degradation indicated growth of the cultures, and subsequent polymer degradation. Reactions of polyDADMAC were concluded with a study of the impact of ozone on polyDADMAC. GPC results indicated a significant change in the ozonated polymer peak profile. Analytical methods to determine polyDADMAC residues in water were reviewed and critically evaluated. Methods based on complex formation/spectroscopy suffered from severe limitations and produced no meaningful results, contrary to claims made by previous researchers. Colloid titration based on an established method was promising but required extensive modification for quantitative analysis. Finally four novel methods were developed, including: solid phase extraction, membrane filtration-GPC, the HACH complexation method, and a GPC method with indirect UV detection. The study is concluded with a chemical risk assessment that indicated minimal human health risks associated with the production and use of polyDADMAC. / AFRIKAANSE OPSOMMING:Hierdie studie behels die sintese, eienskappe en kwantitatiewe analise van polidiallielmetielammoniumchloried (polyDADMAC), 'n wateroplosbare polimeer wat wêreldwyd vir drinkwatersuiwering gebruik word. Die belangstelling in hierdie spesifieke polimeer is as gevolg van die wydverspreide gebruik daarvan en die feit dat daar tans onvoldoende eenvoudige analitiese metodes daarvoor bestaan. Dit is veral belangrik vir waterbehandelingsorganisasies. 'n Nuwe gelpermeasiechromatografie (GPC) metode is ontwikkel en geevalueer vir die analise van hierdie polimeer. Die omvang van die studie is later uitgebrei om die teenwoordigheid van ongereageerde monomeer (DADMAC) asook die persentasie aktiewe polimeer te bepaal. polyDADMAC is eers volgens 'n bekende sintesemetode berei. Die produk is gesuiwer en gekarakteriseer m.b.v. GPC en 13C-KMR. Nuwe bewyse vir die bestaan van 'n vyflid pirollidoonringsisteem is verkry. 'n Meganisme vir hierdie polimerisasie metode is vasgestel. Die aktiwiteit van die bereide polyDADMAC is geevalueer en daar is bevind dat dit effektief as koaguleermiddel optree. Daarna is die chemiese en fisiese eienskappe van polyDADMAC onder gesimuleerde waterbehandelingskondisies bepaal. polyDADMAC het met chloor gerageer om trihalogeneerde metaanverbindings (THMs) te vorm. Gaschromatografie–massa-spektrometrie (GC–MS) is gebruik om die ontstaan van chloroform te bevestig. Daarna is die stabiliteit van die polimeer onder verskei reaksiekondisies bepaal: hitte, UV-bestraling, en pH. GPC-resultate het aangeduiui dat polyDADMAC baie stabiel is en ondergaan strukturele veranderings slegs onder uiterste kondisies van pH, temperatuur en UV. 'n Kort studie van die effek van mikro-organismes op polyDADMAC het egtermikrobiese kultuurgroei met die gevolglike afbreek van die polimeer getoon. Resultate van 'n studie van die impak van osoon op polyDADMAC het getoon dat daar 'n groot verandering in die GPC-profiel van die ge-osoneerde vorm van die polimeer was. Verdere analitiese metodes wat al gebruik is om polyDADMAC residue in water te bepaal, is uitgevoer en krities geevalueer. Metodes gebasseer op kompleksvorming/ spektroskopie het erge beperkings gehad en het nie betekenisvolle resultate gelewer nie. Dit was in teenstelling met wat voorheen deur ander navorsers bevind is. 'n Kolloiedtitrasie gebasseer op 'n bestaande metode het goeie resultate gelewer maar het omvattende veranderings benodig om kwantitatiewe resultate te lewer. Ten slotte is vier nuwe metodes ontwikkel: soliede fase-ekstraksie, membraanfiltrasie-GPC, die HACH-komplekseringsmetode, en 'n GPC-metode met indirekte UV-waarneming.. Die studie is afgesluit met 'n bepaling van die chemiese risiko wat poly DADMAC vir die gesondheid van die mens inhou. Daar is tot die gevolgtrekking gekom dat die produksie en gebruik van poly DADMAC slegs‘n minimum gesondheidsrisiko inhou.

Poor aqueous solubilities of drug candidates limit the biopharmaceutical usefulness in either oral or parenteral dosage forms. Lipid assemblies, such as micelles, may provide a means of enhancing solubility. Despite their usefulness, little is known about the means by which micelles accomplish this result. The goal of the current dissertation is to provide the molecular level understanding of the mechanism by which simple micelle systems solubilize drugs. Specifically, the location, orientation and amount of the drug molecules in micelle systems are the focuses of the work. Three series of model drugs, steroids, benzodiazepines and parabens, in three surfactant systems with anionic, cationic and neutral hydrophilic headgroups were studied. Solubilization power of each micelle system for each model drug was determined by equilibrium solubility. The observed strong surface activities of model drug at hydrocarbon/water interface and the ability of the drugs to compete with surfactants for the model oil/water interface lend support to the hypothesis that drug molecules are mainly solubilized in the interfacial region of the micelles. A surface-localized thermodynamic model that considered the surfactant-drug competition at micelle surface was successfully applied to predict the micelle/water partitioning coefficients. The predictions were made without the use of adjustable parameters in the case of both dilute and concentrated solutions. The orientation of drug at micelle surface was determined by matching calculated occupied areas by solutes at oil/water interface using molecular modeling method to the experimental values. To look into the micro-structure of micelles, twodimensional and diffusion (or PGSE) NMR techniques were employed to detect the specific drug-surfactant interactions and the micelle sizes influenced by model drugs and electrolytes.

The majority of pharmacologically active chemotherapeutics are poorly water soluble. Solubilization enhancement by the utilization of organic solvents often leads to adverse side effects. Nanoparticle-based cancer therapy, which is passively targeted to the tumor tissue via the enhanced permeation and retention effect, has been vastly developed in recent years. Nanocrystals, which exist as crystalline and carry nearly 100% drug loading, has been explored for delivering antineoplastic agents. Additionally, the hybrid nanocrystal concept offers a novel and simple way to integrate imaging agents into the drug crystals, enabling the achievement of theranostics. The overall objective of this dissertation is to formulate both pure and hybrid nanocrystals, evaluate their performance in vitro and in vivo, and investigate the extent of tissue distribution and tumor accumulation in a murine model. Pure and hybrid nanocrystals of several model drugs, including paclitaxel (PTX), camptothecin, and ZSTK474, were precipitated by the antisolvent method in the absence of stabilizer, and their size was further minimized by homogenization. The nanocrystals of PTX, which is the focus of the study, had particle size of approximately 200 nm and close-to-neutral surface charge. Depending on the cell type, PTX nanocrystals exerted different level of cytotoxicity. In human colon and breast cancer xenograft models, nanocrystals yielded similar efficacy as the conventional formulation, Taxol, at a dose of 20 mg/kg, yet induced a reduced toxicity. Biodistribution study revealed that 3H-PTX nanocrystals were sequestered rapidly by the macrophages upon intravenous injection. Yet, apparent toxicity was not observed even after four weekly injections. The sequestered nanocrystals were postulated to be released slowly into the blood circulation and reached the tumor. Tritium-labeled-taxol, in contrast, was distributed extensively to all the major organs, inducing systemic toxicity as observed in significant body weight loss. The biodistribution results obtained from radioactive analysis and whole-body optical imaging was compared. To some degree, the correlation was present, but divergence in the quantitative result, due to nanocrystal integrity and limitations associated with the optical modality, existed. Despite their promising properties, nanocrystal suspensions must be securely stabilized by stealth polymers in order to minimize opsonization, extend blood-circulation time, and efficiently target the tumor.

Monodispersed microgels composed of poly-acrylic acid (PAAc) and poly(N-isopropylacrylamide) (PNIPAM) interpenetrating networks were synthesized by 2-step method with first preparing PNIPAM microgel and then polymerizing acrylic acid that interpenetrates into the PNIPAM network. The semi-dilute aqueous solutions of the PNIPAM-PAAc IPN microgels exhibit an inverse thermo-reversible gelation. Furthermore, IPN microgels undergo the reversible volume phase transitions in response to both pH and temperature changes associated to PAAc and PNIPAM, respectively. Three applications based on this novel hydrogel system are presented: a rich phase diagram that opens a door for fundamental study of phase behavior of colloidal systems, a thermally induced viscosity change, and in situ hydrogel formation for controlled drug release. Clay-polymer hydrogel composites have been synthesized based on PNIPAM gels containing 0.25 to 4 wt% of the expandable smectic clay Na-montmorillonite layered silicates (Na-MLS). For Na-MLS concentrations ranging from 2.0 to 3.2 wt%, the composite gels have larger swelling ratio and stronger mechanical strength than those for a pure PNIPAM. The presence of Na-MLS does not affect the value of the lower critical solution temperature (LCST) of the PNIPAM. Surfactant-free hydroxypropyl cellulose (HPC) microgels have been synthesized in salt solution. In a narrow sodium chloride concentration range from 1.3 to 1.4 M, HPC chains can self-associate into colloidal particles at room temperature. The microgel particles were then obtained in situ by bonding self-associated HPC chains at 23 0C using divinyl sulfone as a cross-linker. The volume phase transition of the resultant HPC microgels has been studied as a function of temperature at various salt concentrations. A theoretical model based on Flory-Huggins free energy consideration has been used to explain the experimental results. Self-association behavior and conformation variation of long chain branched (LCB) poly (2-ethyloxazoline) (PEOx) with a CH3-(CH2)17 (C18) modified surface are investigated using light scattering techniques in various solvents. The polymer critical aggregation concentration (cac) strongly depends on solvent polarity, decreasing as the solvent becomes more hydrophobic.