Hydrogels are three dimensional, insoluble, porous and crosslinked polymer networks. Due to their high water content, they have great resemblance to natural tissues, and therefore, demonstrate high biocompatibility. The porous structure provides an aqueous environment for the cells and also allows influx of nutrients needed for cellular viability. In this study, a natural biodegradable material, agarose (Aga), was used and semi-interpenetrating networks (semi-IPN) were prepared with polymers having different charges, such as positively charged chitosan (Ch) and negatively charged alginate (Alg). Hydrogels were obtained by the thermal activation of agarose with the entrapment of Ch or Alg in the Aga hydrogel structures. Chemical composition of hydrogels were determined by ATR-FTIR examinations, mechanical properties of hydrogels were examined through compression tests, morphologies were confirmed by scanning electron microscopy (SEM) and confocal microscopy, thermal properties were evaluated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Moreover, swelling ratios, water contact angles and surface free energies (SFE) were determined. Cell proliferation and cell migration within these hydrogels were examined by using L929 fibroblast cell line. MTS assays were carried out to observe the cell proliferation on hydrogels. Confocal microscopy was used in order to examine the cell behavior such as cell attachment and cell migration towards the hydrogels. It was observed that addition of positively charged Ch into agarose increased the ultimate compressive strength (UCS), decreased elastic modulus (E), increased the thermal stability and hydrophobicity of the semi-IPN hydrogels. On the other hand, addition of negatively charged Alg into agarose decreased UCS, E, thermal stability and hydrophilicity. Cell-material interaction results showed that Aga hydrogels in tissue engineering applications was improved by adding different charged polyelectrolytes. Cell migration within Aga hydrogels was enhanced by adding Ch, and hindered by addition of Alg. Maximum cell proliferation and maximum penetration of the cells were obtained with the Ch/Aga hydrogels most probably due to attraction between the negatively charged cell surface and the positively charged Ch/Aga hydrogel surface. It was shown that cell interaction of agarose hydrogel scaffolds could be enhanced by introducing chitosan within the agarose hydrogels and obtained structures could be candidates for tissue engineering applications.

The effects of edible chitosan coating on quality factors of pomegranate (Punica granatum) arils were investigated in the present research. For that purpose, pomegranate arils were treated with 0% (control) and 1% chitosan (extracted from shrimp shells and deacetylated (.75%)) solutions and stored at 4

By mixing different stoichiometric ratios of chitosan with alginic acid (AA) and chitosan with p(toluenesulfonicacid) (PTSA), two new polymer networks were prepared. FT-IR spectroscopy results show the protonation of chitosan by AA and PTSA. Elemental analysis (EA) results show the composition of the networks. Thermal gravimetry analysis (TGA) and differential scanning calorimetry (DSC) results were used to characterize the thermal stability of the networks. Then, cholesterol oxidase (ChOx) enzyme were immobilized in these networks and checked for potential use of these enzyme entrapped polymer networks (EEPN) for enzyme immobilization. Additionally, the maximum reaction rate (Vmax) and Michaelis-Menten constant (Km) were evaluated for immobilized ChOx in these two polymer networks. Also, temperature and pH optimization, operational stability, shelf-life and the proton conductivity of these networks were investigated.

The constitutive studies of this thesis were achieved and presented in three parts. In the first part, the effects of solid state synthesis process parameters and the impurity content of primary calcium precursor on the cement-type hydration efficiency for the conversion of &alpha / -tricalcium phosphate (Ca3(PO4)2 or &alpha / -TCP) into hydroxyapatite (Ca10-xHPO4(PO4)6-x(OH)2-x x = 0&ndash / 1, or HAp) have been investigated (at 37&deg / C). &alpha / -TCP was synthesized by thermal processing of stoichiometric amounts of calcium carbonate (CaCO3) and monetite (CaHPO4) at 1150&ndash / 1350&deg / C for 2 h. Three commercial grade CaCO3 powders of different purity were used as starting materials for the synthesis process and the resultant &alpha / -TCP products for all synthesis routes were compared in terms of the material properties and their reactivities. In the second part of the studies, &alpha / -TCP and chitosan fiber (CF) composites were prepared as injectable bone cement systems which have a potential to degrade in time to be replaced by the natural bone tissue. &alpha / -TCP/CF composites were prepared in different compositions and the effect of CF addition on cement properties were examined by mechanical and injectability tests as well as microstructural and phase analysis studies. In the third part of the studies, metal chelating property of CFs was used on development of controlled zinc release systems that can be applied in local zinc deficiency therapies of bone tissue. For this purpose, CF scaffolds were prepared by wet-spinning technique and appropriate amount of zinc was loaded to these scaffolds in regard to the zinc content of a healthy human bone tissue. Zinc release studies were performed on calcium phosphate (CaP) covered and non-covered CF scaffolds and zinc ion concentrations of the release solutions were determined by ICP-MS.

Chitosan is widely investigated for biomedical applications due to its excellent properties, such as biocompatibility, biodegradability, bioadhesivity, antibacterial, etc. In the field of neural engineering, it has been extensively studied in forms of film and hydrogel, and has been used as scaffolds for nerve regeneration in the peripheral nervous system and spinal cord. One of the main issues in neural engineering is the incapability of neuron to attach on biomaterials. The present study, from a new aspect, aims to take advantage of the bio-adhesive property of chitosan to develop chitosan-based materials for neural engineering, specifically in the fields of brain repair and neuroprosthetics. Neuronal responses to the developed biomaterials will also be investigated and discussed.In the first part of this study (Chapter II), chitosan was blended with a well-studied hydrogel material (agarose) to form a simply prepared hydrogel system. The stiffness of the agarose gel was maintained despite the inclusion of chitosan. The structure of the blended hydrogels was characterized by light microscopy and scanning electron microscopy. In vitro cell studies revealed the capability of chitosan to promote neuron adhesion. The concentration of chitosan in the hydrogel had great influence on neurite extension. An optimum range of chitosan concentration in agarose hydrogel, to enhance neuron attachment and neurite extension, was identified based on the results. A “steric hindrance” effect of chitosan was proposed, which explains the origin of the morphological differences of neurons in the blended gels as well as the influence of the physical environment on neuron adhesion and neurite outgrowth. This chitosan-agarose (C-A) hydrogel system and its multi-functionality allow for applications of simply prepared agarose-based hydrogels for brain tissue repair.In the second part of this study (Chapter III), chitosan was blended with graphene to form a series of graphene-chitosan (G-C) nanocomposites for potential neural interface applications. Both substrate-supported coatings and free standing films could be prepared by air evaporation of precursor solutions. The electrical conductivity of graphene was maintained after the addition of chitosan, which is non-conductive. The surface characteristic of the films was sensitively dependent on film composition, and in turn, influenced neuron adhesion and neurite extension. Biological studies showed good cytocompatibility of graphene for both fibroblast and neuron. Good cell-substrate interactions between neurons and G-C nanocomposites were found on samples with appropriate compositions. The results suggest this unique nanocomposite system may be a promising substrate material used for the fabrication of implantable neural electrodes. Overall, these studies confirmed the bio-adhesive property of chitosan. More importantly, the developed chitosan-based materials also have great potential in the fields of neural tissue engineering and neuroprosthetics.

Coating of fine pthesiss to produce tailored surface properties is currently a key development for supercritical fluids applications, in different areas such as: pharmaceutical, nutraceutical, cosmetic, agrochemical, electronic and specialty chemistry industries. During the encapsulation process the pthesis surface can be designed with specific properties by spreading a thin film coating material over the surface of the pthesiss. Chitosan, a natural polymer, was used in this work as the encapsulant material. Chitosan is biocompatible, biodegradable to normal body constituents, safe, non-toxic, bacteriostatic, anticancerogen, and versatile polymer. These attributes are among the properties that make Chitosan an attractive component of pharmaceutical products. The main objective of this research was to encapsulate solid pthesiss under 5fÝm with a biopolymer, Chitosan, using supercritical CO2 as one of the solvents. In order to reach this goal, some the following initial tasks were completed: the cloud point for the system DMSO-CO2 was determined and compared with published data to validate the experimental system. Subsequently the cloud point experiments were extended to include the ternary system Chitosan-DMSO-CO2, and a dynamic solubility experimental set-up was constructed and used to obtain solubility data for the same ternary system. A novel SCF fluidized bed was used to micro encapsulate porous (TiO2) and non-porous pthesiss (CaO) through a temperature swing with a Chitosan thin layer. DMSO was used as an entrainer to enable solubilization of Chitosan and removed within the supercritical carbon dioxide. Several analytical methods were used to characterize these pthesiss; SEM-EDS analysis was used to evaluate a group of pthesiss, determining composition and pthesis diameter on samples up to 900 pthesiss. TEM and AFM confirmed pthesiss of one micron or less were encapsulated with a thickness of less than 5 nm. AFM shows pthesis roughness on the nanometer range, 46 nm or more for uncoated pthesiss and 2-4 nm for the encapsulated ones. FTIR, NMR and DSC-TGA analysis confirmed that the chemical structure of Chitosan remained constant before and after processing, and the changes observed were attributed to some DMSO and moisture adsorbed during the encapsulation process.

Azobenzene based photochromics have been studied widely since the development of the first azo dye, Mauvine, by Perkin in 1856. Azo based dyes have been widely used in industry for over a century. The desire to study them arose from their ease of synthesis and the wide availability of colours which can be tuned by manipulation of the chromophores on the azo molecule itself. The ability of azobenzene to photoisomerise between trans and cis states is widely known. The change in dipole moment affords the ability to fine-tune surfaces via photoisomerisation of the azo molecule. The objective of this investigation was to alter the surface properties of a variety of substrates via the photoisomerisation reaction of several perfluoroalkyl derived azobenzene compounds. These compounds are novel and are based on the idea of the fluoroalkyl chain creating a superhydrophobic surface, similar to Teflon, which would change surface energy upon isomerisation of the azobenzene molecule to give a more hydrophilic surface. This would ultimately then be utilised to coat a fabric surface to provide a photosensitive coating. The compounds used in this work (Admat 1 and 2 and Cfam derivatives) were synthesised in order for their photochemistry in solution and on surfaces to be investigated. The studies began with the photoisomerisation investigations in solution and the calculation of the rate constant and finally the activation energies of these compounds in a variety of common solvents. Interesting results were observed in polar protic solvents which were investigated further. The discovery that aggregation occurred in polar protic solvents due to solubility issues, which in turn led to a fast rate constant was a key finding of the solution work. The surface studies began with the investigation of cellulose as a substrate due to the structural similarity it has with cotton. The azo compounds were derivatised using cyanuric chloride to afford a triazinyl group which was able to attach to the surface of the cellulose via the hydroxyl groups on the surface.

Post-weaning diarrhea is a major health challenge in the swine industry and is routinely managed by fortifying pig starter diets with antimicrobials. But there are concerns about antibiotic resistance, hence the need for identifying effective alternatives. The use of spray-dried whole egg powder containing anti-F4 antibodies (SDWE) against recombinant F4 antigens and chitosan oligosaccharide and Enterococcus fecalis probiotic combination (CPRO) was investigated in two trials using enterotoxigenic Escherichia coli K88+ (ETEC) oral challenge model in 21-d-old piglets. Pre-challenge, SDWE supported higher (P < 0.05) piglet performance whereas during the post-challenge period, SDWE and CPRO had no effect on growth performance but diarrhea incidences and severity were reduced (P > 0.05) in SDWE-fed piglets compared to the control. The results show that SDWE supported greater piglet performance pre-ETEC challenge although there was no benefit of SDWE or CPRO supplementation evident during the post-challenge period in early-weaned pigs. / October 2015

Localized drug delivery is emerging as an effective technique due to its ability to administer therapeutic concentrations and controlled release of drugs to cancer sites in the body. It also prevents the contact of harsh chemotherapy drugs to healthy regions in the body that otherwise would become exposed to current treatments. This study reports on a model chemotherapy drug delivery system comprising non-ionic surfactant vesicles (niosomes) packaged within a temperature-sensitive chitosan network. This smart packaging, or package-within-a package system, provides two distinct advantages. First, the gel prevents circulation of the niosomes and maintains delivery in the vicinity of a tumor. Secondly, the chitosan network protects the niosomes against fluctuations in tonicity, which affects delivery rates. Tonicity is the sum of the concentrations of the solutes which have the capacity to exert an osmotic force across the membrane. Release rates were monitored from both bare niosomes alone and niosome-embedded, chitosan networks. It was observed that chitosan networks prolonged delivery from 100 hours to 55 days in low ionic strength environment and pH conditions similar to a tumor site. The primary effect of chitosan is to add control on release time and dosage, and stabilize the niosomes through a high ionic strength surrounding that prevents uncontrolled bursting of the niosomes. Secondary factors include cross-link density of the chitosan network, molecular weight of the individual chitosan polymers, dye concentration within the niosomes, and the number density of niosomes packaged within the chitosan network. Each of these factors can be altered to fine-tune release rates. Release rate experiments were conducted with 5,6-carboxyfluorescein, a fluorescent dye and chemotherapeutics paclitaxel and carboplatin. In vitro studies showed a preferential affinity of the smart packaged system to ovarian carcinoma cell line OV2008 as compared to normal epithelial cell lines of Ilow and MCC3. Further, feasibility of the drug delivery system was evaluated in vivo. Toxicity studies revealed that the system was non-toxic and feasible in vivo. The final outcome of this study includes tuning of the variables mentioned above that will contribute to the development of low cost and improved methods for drug delivery with application to intracavitary ovarian cancer treatment and other types of cancer

Thesis (MTech. degree in Pharmaceutical Sciences)--Tshwane University of Technology, 2010. / Investigates the absorption enchancing properties of N-trimethyl chitosan chloride (TMC) and monocaprin (MC), individually and in combination, on the permeability of insulin across the Caco-2 intestinal epothelial cell line.