Termiskt expanderbara mikrosfärer är ihåliga polymera partiklar i vilka en flyktig drivgas har kapslats in. När mikrosfärerna upphettas förgasas drivgasen, vilket ökar trycket i mikrosfärerna så att de expanderar och deras volym ökar avsevärt. Denna unika egenskap gör att expanderade mikrosfärer har en låg densitet och är lämpliga för applikationer där låg vikt är väsentligt, och för att förändra ytstrukturer, så som i till exempel konstläder och textiler. Syftet med denna studie har varit att utveckla ett stabilt system för suspensionspolymerisation för att ge en liten mikrosfär (~20 μm efter expansion) som expanderar vid relativt höga temperaturer. Detta har uppnåtts genom att undersöka effekterna av förändringar i stabiliseringssystemet. Komponenterna som varierades var mängden silika (LX), kondensationsoligomeren mellan adipinsyra och dietanolamin (KO), olika formuleringar och mängd av dilauryl peroxid, samt mängden m(III)nitrat. Ytterligare tester gjordes runt effekten av tvärbindning, tillsats av monomeren metyl metakrylat (MMA), samt tillsats av salt (NaCl). Ett stabilt system för polymerisation i 1L-skala med en homogen dispersion uppnåddes med en av dilauryl peroxide formuleringarna tillsammans med en större mängde LX och KO. Studien visar även att kvoten mellan LX och KO har en signifikant effekt på systemets stabilitet och att mängden av både LX och KO påverkar partikelstorleken. / Thermally expandable microspheres are hollow polymeric particles in which a blowing agent has been encapsulated. Upon heating the blowing agent will vaporize, causing the internal pressure to increase, thereby expanding the microspheres. This unique expandable property reduces the density of the microspheres tremendously and makes them excellent for many applications, as for example as light weight fillers and to alter surface textures, such as in artificial leather and textiles. The purpose of this study has been to develop a viable system for the suspension polymerization of a small microsphere (~20 μm when expanded) expanding at fairly high temperatures. This has been accomplished by investigating the effect of changes in the stabilization system. Components of the stabilization system that have been varied were the amounts of silica (LX), condensation oligomer from adipic acid and diethanol amine (KO), and m(III)nitrate, as well as different formulations and amounts of the initiator dilauryl peroxide. Additional tests were performed concerning the effect of the crosslinking, adding the monomer methyl methacrylate (MMA), and the addition of salt (NaCl). A system for polymerization in 1L-scale was accomplished where it was found that one of the dilauryl peroxide formulations together with a higher amount of LX and KO provided a stable system giving homogeneous dispersions in which the microspheres have the desired expansion properties. Also, the ratio between LX and KO had a significant effect on the stability of the system and the amount of both LX and KO affects the particle size.

Thermally expandable microspheres are spherical particles around 5-­‐40 µm in size, consisting of a polymeric shell in which a blowing agent has been encapsulated. The microspheres are expanded upon heating, resulting in a particularly low density. Microspheres are therefore suitable to use as light weight filler or as foaming agent. AkzoNobel is world leading in the production of expandable microspheres, which are commercialised under the name Expancel. Sustainability is a great focus at AkzoNobel and two issues that AkzoNobel works with today is to develop products free from chlorine and Me1. The aim with this thesis has been to investigate whether it is possible to produce microspheres free from these chemicals and to see if they can be a more sustainable alternative to one of the existing Expancel grades. In this study, the microspheres have been produced through free radical suspension polymerisation and analysed by measuring mainly the particle size and expansion properties. The polymeric shell was composed of the monomers acrylonitrile, methacrylonitrile, and methyl acrylate. The main focus has been to evaluate the silica-­‐based stabilisation system, which stabilise the monomer droplets during the suspension polymerisation. The stabilisation is possible due to the formation of silica flocs that is adsorbed on the surface of the droplets. It has been investigating how different parameters, e.g. amount of stabiliser or mixing procedure, affects the formation of silica flocs and the stabilisation of monomer droplets. For the silica-­‐based system, it was found that the mixing order, stirring rate, and amount of stabilisers affect the formation of flocs. It was also seen that the amount of stabiliser affect the stabilisation of droplets, and that some stabilisers is more significant than others. Microspheres without chlorine and Me1 have successfully been produced in laboratory scale (50 mL and 1 L). The expansion and size of the microspheres produced in this study was relatively similar to one of the existing Expancel grades. However, the reproducibility of polymerisations in 1 litre reactors has been poor. / Termiskt expanderbara mikrosfärer är sfäriska partiklar, ca 5-­‐40 µm i diameter, som består av ett polymerskal som innesluter en drivgas. Mikrosfärerna expanderar när de utsätts för värme och erhåller då en mycket låg densitet. De är därför lämpliga att använda som fyllmedel då låg vikt är önskvärt eller som skummedel. AkzoNobel är världsledande inom produktion av expanderbara mikrosfärer, som marknadsförs under namnet Expancel. Hållbar utveckling är en viktig fråga för AkzoNobel och två problem som de står inför idag är att utveckla produkter fria från klor och Me1. Målet med detta examensarbete har varit att undersöka om det är möjligt att framställa mikrosfärer fria från dessa kemikalier och om de framtagna mikrosfärerna skulle kunna vare ett hållbarare alternativ till en av de befintliga Expancel-­‐ produkterna. I den här studien har mikrosfärerna framställts genom suspensionspolymerisation som initierats av fria radikaler och de har analyserats främst genom att mäta partikelstorlek och expansionsegenskaper. Polymerskalet bestod av monomererna akrylnitril, metakrylnitril och metylakrylat. I det här arbetet har det viktigaste varit att utvärdera det silikabaserade stabiliseringssystemet som stabiliserar monomerdropparna vid polymerisationen. Stabiliseringen är möjlig eftersom silika bildar flockar som adsorberar på ytan av monomerdropparna. Olika parametrar, exempelvis mängd stabiliseringsmedel och satsningsförfarande, har därför varierats för att undersöka vilken effekt det får på flockningen av silika och stabiliseringen av monomerdroppar. Satsningsordning och omrörningshastiget för stabiliseringssystemet samt mängd stabiliseringsmedel är några av de faktorer som påverkar bildningen av flockar. Det konstaterades även att mängd stabiliseringsmedel påverkar stabiliseringen utav monomerdropparna. Fulländade mikrosfärer utan klor och Me1 har framställts i laboratorieskala (50 mL och 1 L) och partikelstorleken samt expansionsegenskaper är jämförbara med en av Expancels nuvarande produkter. Dock har reproducerbarheten i 1 litersskala varit otillfredsställande.

At Nouryon Stockvik the Expancel production site is located. Expandable microspheres areused in for many types of applications and is a technically challenging product. At ExpancelStockvik they are constantly striving to improve product properties in line with customerexpectations. To be able to do this, it is important to understand the properties of themicrospheres such as crystallinity and crystallite size.Films was prepared from microspheres dissolved in DMA and analyzed with High-resolutionSEM, Powder X-Ray Diffraction and Raman Spectroscopy. The aim was to develop a methodto investigate and determine crystalline ratios and crystallite size within the microsphere filmsand the microspheres before film preparation. The eventual correlation between morphologyand crystallinity was also studied. An attempt of finding an amorphous reference sample wasalso performed, this was done by grinding microspheres in liquid nitrogen, unfortunately, nosuccess was reached. Gauss-fitting was therefore performed to be able to find the amorphousregions of the XRD Diffractogram for the calculations of crystallinity and crystallite size. TheGauss-fitting was successfully performed with good R-square values.During the Raman analysis some fluorescence problems occurred, this problem will probablybe solved if a laser source with higher excitation frequency is used in future analysis. Evenwith fluorescence problems, Raman analysis could successfully be performed and giveinformation of the composition. The crystallite size was in general larger for the microspheresbefore they were prepared from dissolving them to make films. Generally, it seems as there isa correlation between the morphology, crystallinity, and crystallite size.

Background: Spinal cord injury (SCI) is a devastating condition for which current treatment strategies provide no cure. Delivery of growth factors at the injury site may stimulate endogenous stem cells for nerve regeneration. Biocellulose (BC) was reported to be biocompatible, abundant and have adjustable mechanical properties. However, BC has not been tested for the treatment of SCI. Hypothesis: Composite microsphere loaded BC tubes can have a sustained protein release profile with high encapsulation efficiency and low initial burst rendering it suitable for spinal cord regeneration. Methods: Bovine serum albumin loaded poly (lactic-co-glycolic acid) microspheres were fabricated and characterized while studying the effect of different process parameters on encapsulation efficiency, release profile and morphology. Microspheres were loaded to BC tubes and were characterized morphologically and mechanically. Results: Inner phase volume and the drug:polymer ratio are the main factors impacting microsphere protein encapsulation. Furthermore, presence of different osmotic agent concentrations in the aqueous phase produced a smooth morphology while eliminating the initial burst. Finally, the composite BC tubes were fabricated, and mechanical properties were suitable for SCI applications. Contexte : Les lésions de la moelle épinière sont une maladie dévastatrice que les stratégies de traitement actuelles ne permettent pas de guérir. L'administration de facteurs de croissance sur le site de la lésion peut stimuler les cellules souches endogènes pour la régénération des nerfs. La biocellulose est biocompatible, abondante et possède des propriétés mécaniques ajustables. Cependant, la biocellulose n'a pas été testée pour le traitement des lésions de la moelle épinière. Hypothèse : Les microsphères en composite situées dans les tubes de biocellulose peuvent avoir un profil de libération soutenue de protéines avec une grande efficacité d'encapsulation ainsi qu’un faible taux de libération initial, ce qui les rend appropriés pour la régénération de la moelle épinière. Méthodes : Des microsphères de poly (acide lactique-co-glycolique) chargées d’albumine de sérum bovin ont été fabriquées et caractérisées tout en étudiant l'effet de différents paramètres du processus sur l'efficacité de l'encapsulation, le profil de libération et la morphologie. Les microsphères ont été mises dans des tubes de biocellulose et ont été entièrement caractérisées. Résultats : Le volume de la phase interne et le ratio médicament : polymère sont les principaux facteurs qui influent sur l'encapsulation des protéines en microsphères. De plus, la présence de différentes concentrations de sel dans la phase aqueuse a produit une morphologie lisse tout en éliminant la libération initiale. Enfin, les tubes de biocellulose en composite ont été fabriqués et les propriétés mécaniques étaient adaptées pour l’application sur des lésions de la moelle épinière.

Aqueous industrial effluents containing organic pollutants, such as textile dyes and crude oil, represent environmental and human health concerns due to their toxicity and possible carcinogenic effects. Adsorption is the most promising wastewater treatment method due to its efficiency, ease of operation, and low cost. However, currently used adsorbents have either high regeneration costs or low adsorption capacities. In this work, new organic/inorganic hybrids based on hollow silica microspheres were successfully synthesized, and their ability to remove Methylene Blue from wastewater and crude oil from simulated produced water was evaluated. By employing four different silanes, namely triethoxy (octyl) silane, triethoxy (dodecyl) silane, trichloro (octadecyl) silane, and triethoxy (pentafluorophenyl) silane, hydro and fluorocarbons were grafted onto the surface of commercially available silica microspheres. These silica derivatives were tested as adsorbents by exposing them to Methylene Blue aqueous solutions and synthetic produced water. Absorbance and oil concentration were measured via a UV/Vis Spectrophotometer and an HD-1000 Oil-in-Water Analyzer respectively. Methylene Blue uptake experiments showed that increasing the adsorbent dosage and decreasing initial dye concentration might increase adsorption percentage. On the other hand, adsorption capacities were improved with lower adsorbent dosages and higher initial dye concentrations. Varying the initial solution pH, from pH 5 to pH 9, and increasing ionic strength did not seem to have a significant impact on the extent of adsorption of Methylene Blue. Overall, the silica derivative containing aromatic functional groups, Caro, was proven to be the most effective adsorbent due to the presence of π-π and cation-π interactions in addition to the van der Waals and hydrophobic interactions occurring with all four adsorbents. Although the Langmuir Model did not accurately represent the equilibrium data, it produced consistent maximum adsorption values and adsorption equilibrium constants. Preliminary experiments demonstrated the potential to recover and reuse the silica microspheres by washing with NaOH and organic solvents. The preferential adsorption of oil micro-droplets onto the surface of functionalized hollow silica microspheres was evidenced. However, preparing synthetic produced water that was stable enough to carry out kinetics experiments remained a challenge.

No description available.

Bone is currently the second most transplanted tissue, second only to blood. However, significant hurdles including graft supply and implant failure continue to plague researchers and clinicians. Currently, standard clinical procedures include autologous and allogeneic grafting. Autologous grafts may achieve functional repair; yet, they are available in limited supply and are associated with donor site morbidity. Allogeneic grafts are available in greater supply, but have a higher risk of infection. To overcome the disadvantages of current grafts, tissue engineering has become a major focus for the regeneration of bone. The goal of tissue engineering is to use a multidisciplinary approach to create biomimetic constructs that stimulate osteogenic regeneration to heal bone defects and restore tissue function. Biodegradable scaffolds are used in tissue engineering strategies as an interim template for tissue regeneration. The scaffold architecture provides mechanical support for cell attachment and tissue regeneration. Biocompatible poly(lactic-co-glycolic acid) (PLGA) has been processed through a number of techniques to create porous 3D architectures. Hydroxyapatite (HAP) and tricalcium phosphate have been used in conjunction with polymer scaffolds due to their osteoconductivity and biocompatibility, but they often lack osteoinductivity and are resistant to biodegradation. Conversely, amorphous calcium phosphate (ACP) is a mineral that solubilizes under aqueous conditions, releasing calcium and phosphate ions, which have been postulated to enhance osteoblast differentiation and mineralization. Controlled dissolution can be achieved by stabilizing ACP with divalent cations such as zinc or copper. Furthermore, incorporation of such osteogenic ACPs within a biodegradable PLGA scaffold could enhance the osteoconductivity of the scaffold while providing calcium and phosphate ions to differentiating osteoprogenitor cells, thereby stimulating osteogenesis when implanted in vivo. In this research, the effect of zinc on the differentiation of osteoprogenitor cells was investigated. Zinc supplementation of the culture media had no stimulatory effect on cell proliferation or differentiation. ACPs were synthesized using zirconium (ZrACP) and zinc (ZnACP) as stabilizers to achieve sustained ion release. Elevated concentrations suggested sustained ion release over the course of 96 hours and enhanced solubility of ZrACP and ZnACP. X-ray diffraction analysis showed a conversion of ZrACP to a semi-crystalline material after 96 hours, but ZnACP showed no conversion after 96 hours. Composite scaffolds were fabricated by incorporating HAP, zirconium-stabilized ACP (ZrACP), or zinc-stabilized ACP (ZnACP) into a sintered PLGA microsphere matrix and then characterized to determine the effect of the minerals on the in vitro differentiation of MC3T3-E1 cells. Scanning electron microscopy revealed a porous microsphere matrix with calcium phosphate powders distributed on the surface of the microspheres. Measurements of mechanical properties indicated that incorporation of 0.5 wt% calcium phosphates resulted in a 30% decrease in compressive modulus. When cells were cultured in the scaffolds, composite ACP scaffolds stimulated proliferation and ALP activity, while HAP scaffolds stimulated osteoblast gene expression. Overall, the results of this work indicate the addition of calcium phosphate minerals to PLGA scaffolds supported cell growth and stimulated osteogenic differentiation, making the scaffolds a promising alternative for bone tissue regeneration. / Ph. D.

No description available.

Methods of guiding magnetic particles in a controlled fashion through the arterial system in vivo using external magnetic fields are explored. Included are discussions of applications, magnetic field properties needed to allow guiding based on particle characteristics, hemodynamic forces, the uniformity of field and gradients, variable tissue characteristics, and imaging techniques employed to view these particles while in transport. These factors influence the type of magnetic guidance system that is needed for an effective drug delivery system. This thesis reviews past magnetic drug delivery work, variables, and concepts that needed to be understood for the development of an in vivo magnetic drug delivery system. The results of this thesis are the concise study and review of present methods for guided magnetic particles, aggregate theoretical work to allow proper hypotheses and extrapolations to be made, and experimental applications of these hypotheses to a working magnetic guidance system. The design and characterization of a magnetic guidance system was discussed and built. The restraint for this system that balanced multiple competing variables was primarily an active volume of 0.64 cm3, a workspace clearance of at least an inch on every side, a field of 0.3T, and a local axial gradient of 13 T/m. 3D electromagnetic finite element analysis modeling was performed and compared with experimental results. Drug delivery vehicles, a series of magnetic seeds, were successfully characterized using a vibrating sample magnetometer. Next, the magnetic seed was investigated under various flow conditions in vitro to analyze the effectiveness of the drug delivery system. Finally, the drug delivery system was successfully demonstrated under limiting assumptions of a specific magnetic field and gradient, seed material, a low fluid flow, and a small volume. / Master of Science

Zhang, Xinran. / Thesis submitted in: December 2007. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 80-87). / Abstracts in English and Chinese. / TITLE PAGE --- p.i / ABSTRACT --- p.ii / 中文摘要 --- p.v / ACKNOWLEDGEMENTS --- p.vii / TABLE OF CONTENTS --- p.viii / LIST OF FIGURES --- p.xi / LIST OF TABLES --- p.xiv / ABBREVIATIONS --- p.xv / Chapter CHAPTER 1. --- Introduction / Chapter 1.1. --- Rationale of the Study --- p.1 / Chapter 1.2. --- Current technologies for formulating long-acting parenteral protein deliver system --- p.3 / Chapter 1.2.1. --- Chemical Modification --- p.3 / Chapter 1.2.2. --- Sustained-release formulation --- p.4 / Chapter 1.2.2.1. --- Phase separation method --- p.4 / Chapter 1.2.2.2. --- Solvent evaporation/extraction method --- p.5 / Chapter 1.2.2.3. --- Spray drying method --- p.6 / Chapter 1.2.2.4. --- Causes for protein instability --- p.6 / Chapter 1.2.2.4.1. --- Water/organic solvent interface --- p.6 / Chapter 1.2.2.4.2. --- Lyophilization --- p.8 / Chapter 1.2.2.4.3. --- Polymer --- p.11 / Chapter 1.2.2.4.4. --- Stabilizing additive --- p.13 / Chapter 1.3. --- Aqueous-aqueous emulsion technology --- p.17 / Chapter 1.3.1. --- Background --- p.17 / Chapter 1.3.2. --- Basic Principle --- p.17 / Chapter 1.3.3. --- Phase diagram --- p.18 / Chapter 1.3.4. --- Formation of aqueous-aqueous emulsion --- p.19 / Chapter 1.3.4.1. --- Introduction of a water-soluble charged polymer as stabilizer --- p.19 / Chapter 1.3.4.2. --- Freezing-induced phase separation --- p.20 / Chapter 1.3.5. --- General Protocol --- p.21 / Chapter 1.3.5.1. --- Introduction of a water-soluble charged polymeric stabilizer --- p.22 / Chapter 1.3.5.2. --- Freezing-induced phase separation --- p.22 / Chapter 1.3.6. --- Merits and limitations of the aqueous-aqueous emulsion technology --- p.23 / Chapter 1.3.7. --- Protein selection for the sustained release formulation --- p.25 / Chapter 1.4. --- Aims and scope of study --- p.26 / Chapter "CHAPTER 2," --- Materials and Methods / Chapter 2.1. --- Materials --- p.28 / Chapter 2.1.1. --- Proteins --- p.28 / Chapter 2.1.2. --- Polymers --- p.28 / Chapter 2.1.3. --- Media for TF-1 Cell Culture --- p.28 / Chapter 2.1.4. --- Chemicals and Solvents for Cell Proliferation Assay --- p.29 / Chapter 2.1.5. --- Other Chemicals and Solvents --- p.29 / Chapter 2.1.6. --- Materials for Cell Culture --- p.29 / Chapter 2.1.7. --- Materials for Reagent Kits --- p.30 / Chapter 2.2. --- Methods --- p.30 / Chapter 2.2.1. --- Determination of the Partition Coefficients of Proteins Between PEG and Dextran --- p.30 / Chapter 2.2.2. --- Preparation of Glassy Particles --- p.31 / Chapter 2.2.2.1. --- Standard Stable Aqueous-aqueous Emulsion Method --- p.31 / Chapter 2.2.2.2. --- Freezing-induced Phase Separation --- p.32 / Chapter 2.2.3. --- Preparation of Protein-loaded and Blank Microspheres Using S-o-w Solvent Extraction Technique --- p.32 / Chapter 2.2.4. --- Optical Microscopy and Scanning Electron Microscopy --- p.33 / Chapter 2.2.5. --- Determination of Protein Loading --- p.34 / Chapter 2.2.5.1. --- Within Dextran Particles --- p.34 / Chapter 2.2.5.2. --- Within PLGA microspheres --- p.34 / Chapter 2.2.6. --- Evaluation of Protein Structural Integrity and Bioactivity in Dextran Particles and PGLA Microspheres --- p.35 / Chapter 2.2.7. --- In vitro Release Study --- p.36 / Chapter 2.2.8. --- RhIFN Stability Determination under Simulated In Vitro Release Conditions --- p.37 / Chapter 2.2.8.1. --- In the Absence of PLGA --- p.37 / Chapter 2.2.8.2. --- In the Presence of PLGA --- p.37 / Chapter 2.2.9. --- MicroBCÁёØ Protein Assay --- p.38 / Chapter 2.2.10. --- Size Exclusion Chromatography (SEC) - High Performance Liquid Chromatography (HPLC) --- p.38 / Chapter 2.2.11. --- ELISA --- p.39 / Chapter 2.2.12. --- Bioactivity Assay --- p.40 / Chapter 2.2.12.1. --- RhIFN --- p.40 / Chapter 2.2.12.2. --- RhGM-CSF --- p.41 / Chapter CHAPTER 3. --- Results and Discussions / Chapter 3.1. --- Sustained-release RhIFN Formulation --- p.45 / Chapter 3.1.1. --- Partition Coefficient of RhIFN --- p.45 / Chapter 3.1.2. --- Formulation Based on the Standard Aqueous-aqueous Emulsion (SA-AE) Method With Sodium Alginate as Stabilizer --- p.45 / Chapter 3.1.2.1. --- Surface Morphology --- p.45 / Chapter 3.1.2.2. --- Formulation Characterization --- p.46 / Chapter 3.1.2.3. --- In Vitro Release of RhIFN from PLGA Microsheres --- p.54 / Chapter 3.1.3. --- Formulation Based on the Freezing-induced Phase Separation (FIPS) Technique without Sodium Alginate --- p.56 / Chapter 3.1.3.1. --- Formulation Characterization --- p.56 / Chapter 3.1.3.2. --- In Vitro Release of RhIFN from PGLA Microsphees --- p.59 / Chapter 3.2. --- RhIFN Stability Assessment under Simulated In Vitro Release Conditions --- p.63 / Chapter 3.2.1. --- In the Absence of PLGA --- p.63 / Chapter 3.2.2. --- In the Presence of PLGA --- p.65 / Chapter 3.3. --- Sustained-release RhGM-CSF Formulation --- p.68 / Chapter 3.3.1. --- Partition Coefficient Determination of RhGM-CSF Between PEG and Dextran --- p.68 / Chapter 3.3.2. --- Formulation Based on Freezing-induced Phase Separation --- p.68 / Chapter 3.3.2.1. --- Validation of MTT Assay Conditions --- p.69 / Chapter 3.3.2.2. --- Formulation Characterization --- p.71 / Chapter 3.3.2.3. --- In Vitro Release of RhGM-CSF from PLGA Microspheres --- p.75 / Chapter CHAPTER 4. --- Conclusion and Future Studies / Chapter 4.1. --- Conclusion --- p.78 / Chapter 4.2. --- Future Studies --- p.79 / References --- p.80