No description available.

This thesis is focused on synthesis and polymerization of caprolactone and its derivatives by living ring opening polymerization (LROP), Self-assembly in aqueous solutions produced nanoaggregates comprised of amphiphilic block copolymers or telechelic polymers with incorporated boron compounds (phenyl boronic acids and boron clusters). Incorporation of boron compounds was facilitated either by covalent or non-covalent bonding. Obtained complex nanoparticle structures manifested stimuli-responsive behaviour and were investigated under varying conditions by combination of light scattering, fluorescence spectroscopy and electron microscopy. The obtained results on solution behaviour of polymers in combination with added value of boron compounds, yield general aspects of nano aggregate morphology, responsive character tuning and practical aspects of synthesis and self-assembly overcame in the preparation process. The publications wrote during this thesis are therefore adding valuable information to researchers engaged in biomedical utilization of such nano assemblies.

Bakterier som är resistenta mot antibiotika har de senaste åren blivit ett stort hot mot mänskligheten. Att utveckla nya antibiotikaläkemedel är väldigt tidskrävande samt kommer med en dyr prislapp. Det är några av anledningarna att forskare har inriktat sig på antimikrobiella peptider (AMPs) som ett alternativ till traditionella antibiotika. Dessa peptider finns i alla levande organismer och uppvisar en snabb och ospecifik mekanism. Vidare så är de mindre benägna att utveckla resistens hos bakterierna. Däremot så har dessa AMPar visat sig ha låg stabilitet och en del toxiska biverkningar. Olika typer av nanobärare kan användas för att överkomma dessa kommakortanden. Syftet med denna studie var att utveckla en optimerad nanobärare för AMPen AP114. Peptiden har blivit inkluderad i nanostrukturerade lipidbärare (NLC) samt liposomer. Dessa har producerats med smält emulsifieringsmetod och lösningsinjektion metoden. De fysikalkemiska karaktäristik hos olika blanka samt AP115 laddade nanoformuleringar har analyserats samt jämförts. Resultaten indikerade att liposomformuleringarna hade den lägsta partikelstorleken och storleksfördelning men en kontrollerad in vitro frisättning av peptiden över 48 timmar. Generellt, så indikerar de preliminära resultaten en potential nanoformulering för peptiden AP114. / In the past few years, bacterial resistance to antibiotics has posed a major threat to humankind. Development of substitutes for traditional antibiotics is a highly time consuming and expensive venture. For this reason, researchers are focusing on using antimicrobial peptides (AMP) as an alternate. These peptides are found in all living organisms and exhibit a fast and non-targeted mechanism of action. Besides, they are less susceptible to microbial resistance. However, these therapeutic peptides are not stable and have toxic side effects. To overcome these limitations, drug delivery systems have been explored. In this study, the aim was to develop an optimized drug delivery system for AP114. The peptide has been encapsulated in nanostructured lipid carriers (NLC) and liposomes, produced by melt emulsification method and solvent injection method, respectively. The physicochemical characterization of different blank and AP114 loaded nanoformulations were analyzed and compared. The results indicated the liposome samples to have the lowest particle size distribution and polydispersity, with a controlled in vitro release of the peptide over 48 hours. Overall, these preliminary findings suggest a promising potential for the formulation of a nanocarrier for AP114 peptide.

No description available.

Noble metal nanoparticles such as gold and silver are of interest because of the unique electro-optical properties (e.g., localized surface plasmon resonance [LSPR]) that originate from the collective behavior of their surface electrons. These nanoparticles are commonly developed and used for biomedical and industrial application. A recent report has predicted that the global market for gold nanoparticles will be over 12.7 tons by year 2020. However, these surface-functionalized nanoparticles can be potential environmental persistent contaminants post-use due to their high colloidal stability in the aquatic systems. Despite, the environmental risks associated with these nanoparticles, just a few studies have investigated the effect of nanofeature factors such as size and shape on the overall fate/transport and organismal uptake of these nanomaterials in the aquatic matrices. This study presents a comprehensive approach to evaluate the colloidal stability, fate/transport, and organismal uptake of these nanoparticles while factoring in the size and shape related properties. We demonstrate the importance and effect of anisotropicity of a gold nanoparticle on the colloidal behavior and interaction with ecologically susceptible aquatic biota. We also show how readily available characterization techniques can be utilized to monitor and assess the fate/transport of this class of nanoparticles. We further describe and investigate the relationship between the aspect ratio (AR) of these elongated gold nanoparticles with clearance mechanisms and rates from the aquatic suspension columns including aggregation, deposition, and biopurification. We illustrate how a fresh water filter-feeder bivalve, Corbicula fluminea, can be used as a model organism to study the size and shape-selective biofiltration and nanotoxicity of elongated gold nanoparticles. The results suggest that biofiltration by C. fluminea increases with an increase in the size and AR of gold nanoparticle. We develop a simple nanotoxicity assay to investigate the short-term exposure nanotoxicity of gold nanoparticles to C. fluminea. The toxicity results indicate that for the tested concentration and exposure period that gold nanoparticles were not acutely toxic (i.e., not lethal). However, gold nanoparticles significantly inhibited the activities of some antioxidant enzymes in gill and digestive gland tissues. These inhibitions could directly affect the resistance of these organisms to a secondary stressor (temperature, pathogens, hypoxia etc.) and threaten organismal health. / Ph. D.

Increased proliferation of nanotechnology has led to concerns regarding its implication to the water environment. Gold nanoparticles (AuNP) were used as a model nanomaterial to investigate the fate and dynamics of nanoparticles in the complex water environment. A column study was performed to examine the fate and transport of gold nanoparticles with two different coatings in porous media. The resulting data suggested that gold nanoparticles aggregate significantly in the porespace of the column interior, a finding that is not predicted by traditional colloidal filtration theory or Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Surface-enhanced Raman spectroscopy (SERS) was developed as a new technique to investigate AuNP aggregation in water with varying salt levels. The SERS technique proved valuable as an analytical technique, elucidating information about aggregation as well as AuNP surface interactions with dissolved halides in water. A thorough investigation examining Aunt aggregation with monovalent and divalent salts utilizing SERS, ultraviolet-visible light (UV-Vis) spectroscopy, and dynamic light scattering (DLS) was conducted. Each technique provided data describing different aspects of the dynamic behavior of AuNPs in complex water environments. Results suggest that in addition to attractive and repulsive interactions described by DLVO theory, chemical interactions between the AuNP surface and dissolved halides were also a significant driving force for aggregation and other transformative behaviors of AuNPs in water. The SERS technique developed in this work was shown to be a viable tool to help unveil the vastly complex dynamics of nanomaterial in the water environment. / Ph. D.

La thérapie photodynamique (PDT) constitue une approche prometteuse pour le traitement de tumeurs cancéreuses accessibles à la lumière, en particulier pour la réduction des effets indésirables comparés à la chimiothérapie classique. Particulièrement intéressante pour le traitement du rétinoblastome, cancer le plus fréquent chez le jeune enfant, elle nécessite le développement de nouveaux photosensibilisateurs dont la structure est mieux adaptée aux spécificités des cellules ciblées. Dans le cadre de cette thèse, nous avons étudié des dérivés porphyriniques à structure dendrimérique pour amplifier leur caractère amphiphile et créer un cluster de sucres. Cette structure pourrait favoriser la reconnaissance de ces molécules par des récepteurs membranaires, interactions déjà mises en évidence grâce à des modèles membranaires artificiels. L'objectif de cette thèse était de déterminer les mécanismes d'interactions spécifiques et non spécifiques de ces molécules avec la membrane plasmique et de valider la pertinence des modèles artificiels. Si la culture cellulaire s'est avérée inadaptée pour cette détermination, une approche innovante utilisant une microbalance à cristal de quartz et des expériences de cytométrie en flux ont confirmé la capacité des porphyrines dendrimériques à interagir avec un ou plusieurs récepteurs spécifiques. Une analyse de la composition lipidique des membranes cellulaires de la lignée Y79 et de deux xénogreffes a été également entreprise afin de mieux caractériser ces membranes et de contribuer à l'élaboration d'un modèle lipidique artificiel davantage biomimétique du rétinoblastome. / Photo Dynamic Therapy (PDT) is a promising alternative treatment against solid tumors reachable to light with less side-effects than classical chemotherapies. Its efficacy mainly relies on the physicochemical properties of a photosensitizer (PS), and its penetration into tumour cells. PDT is particularly interisting for the treatment of retinoblastoma, a malignant intraocular tumor affecting young children. Consequently, new photosensitizers need to be created. Since PS uptake may be ease by the over-expression of a mannose receptor at the surface of retinoblastoma cells, amphiphilic dendrimeric porphyrins grafted with mannose groups have been synthetised. Model membranes allow the identification of structural parameters controlling the passive penetration of porphyrins into cells. Specific interactions have been previously shown between these porphyrins and a model membrane grafted with a lectin (Concanavalin A) mimicking the mannose receptor on the retinoblastoma cell membrane. In this work we aimed at i) assessing the relevance of the membrane model with biological studies (cell culture and flow cytometry) and ii) improve the model with a lipidomic analysis of retinoblastoma cells and xenografts. Cell culture revealed to be unsuitable for our studies. To overcome this, we used an innovative approach in which retinoblastoma cells were immobilized onto the sensor of a quartz crystal microbalance (QCM-D). We fully confirmed the results achieved with the artificial membrane model. Since the composition of a membrane plays a crucial role, a lipidomic analysis of Y79 cell and xenografts membranes has been performed. Phospholipids and cholesterol have been identified and quantified with LC-DEDL and GC-MS. The feedback from these experiments not only provided useful information about the differences in lipidic composition of these membranes, but also allowed us to refine the lipidic composition of our models.

The main objective of this thesis work was to gain understanding of the principles of biolubrication, focusing on synergistic effects between biolubricants. To this end surface force and friction measurements were carried out by means of Atomic Force Microscopy, using hydrophilic and hydrophobic model surfaces in salt solutions of high ionic strength (≈ 150 mM) in presence of different biolubricants. There was also a need to gain information on the adsorbed layers formed by the biolubricants. This was achieved by using a range of methods such as Atomic Force Microscopy PeakForce imaging, Quartz Crystal Microbalance with Dissipation, Dynamic Light Scattering and X-Ray Reflectometry. By combining data from these techniques, detailed information about the adsorbed layers could be obtained.The biolubricants that were chosen for investigation were a phospholipid, hyaluronan, lubricin, and cartilage oligomeric matrix protein (COMP) that all exist in the synovial joint area. First the lubrication ability of these components alone was investigated, and then focus was turned to two pairs that are known or assumed to associate in the synovial area. Of the biolubricants that were investigated, it was only the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) that was found to be an efficient lubricant on its own. Deposited DPPC bilayers on silica surfaces were found to be able to provide very low friction coefficients (≈ 0.01) up to high pressures, ≈ 50 MPa. A higher load bearing capacity was found for DPPC in the liquid crystalline state compared to in the gel state.The first synergy pair that was explored was DPPC and hyaluronan, that is known to associate on the cartilage surface, and we also noticed association between hyaluronan and DPPC vesicles as well as with adsorbed DPPC bilayers. By combining these two components a lubrication performance similar to that of DPPC alone could be achieved, even though the friction coefficient in presence of hyaluronan was found to be slightly higher. The synergy here is thus not in form of an increased performance, but rather that the presence of hyaluronan allows a large amount of the phospholipid lubricant to accumulate where it is needed, i.e. on the sliding surfaces.The other synergy pair was lubricin and COMP that recently has been shown to be co-localized on the cartilage surface, and thus suggested to associate with each other. Lubricin, as a single component, provided poor lubrication of PMMA surfaces, which we utilized as model hydrophobic surfaces. However, if COMP first was allowed to coat the surface, and then lubricin was added a low friction coefficient (≈ 0.03) was found. In this case the synergy arises from COMP facilitating strong anchoring of lubricin to the surface in conformations that provide good lubrication performance. / Huvudsyftet med det här avhandlingsarbetet var att öka förståelsen för den låga friktion som finns i vissa biologiska system, med fokus på synergistiska effekter mellan de smörjande molekylerna. För detta ändamål studerades ytkrafter och friktion med hjälp av atomkraftsmikroskopi. Mätningarna utfördes med hydrofila och hydrofoba modellytor i lösningar med hög salthalt (≈ 150 mM) i närvaro av smörjande biomolekyler. Det var också nödvändigt att få information om de adsorberade skikten av biomolekyler. Det åstadkoms med hjälp av en rad tekniker så som AFM PeakForce avbildning, kvartskristallmikrovåg, dynamisk ljusspridning och röntgen reflektometri. Genom att kombinera data från dessa tekniker erhölls detaljerad information om de smörjande skikten.De smörjande biomolekyler som valdes ut för studierna var en fosfolipid, hyaluronan, lubricin, and cartilage oligomeric matrix protein (COMP) vilka alla finns i synovialledsområdet. Först undersöktes den smörjande förmågan hos dessa komponenter var för sig, och sedan fokuserade vi på två par av biomolekyler som man vet eller antar bildar associationsstrukturer i synovialleder. Av de enskilda biomolekyler som undersöktes var det endast fosfolipiden 1,2-dipalmitoyl-sn-glycero-3-fosfokoline (DPPC) som visade sig vara en effektivt smörjande molekyl. Deponerade biskikt av DPPC på silikaytor gav upphov till mycket låga friktionskoefficienter (≈ 0.01) upp till höga pålagda tryck, ≈ 50 MPa. DPPC bilager i flytande kristallin fas visade sig ha högre lastbärande förmåga än DPPC bilager i geltillstånd.Det första synergistiska par som undersöktes var DPPC och hyaluronan vilka man vet associerar på broskytan, och vi visade att hyaluronan associerar med såväl DPPC vesiklar som med DPPC bilager. Genom att kombinera dessa två komponenter uppmättes en smörjande förmåga som var jämförbar med den som DPPC ensam uppvisar. Även om friktionskoefficienten var något högre i närvaro av hyaluronan. Synergieffekten här består inte av en bättre smörjande förmåga, utan istället gör närvaron av hyaluronan att de smörjande fosfolipiderna kan ansamlas i stora mängder där de behövs, dvs. på de glidande ytorna.Det andra synergiparet var lubricin och COMP vilka nyligen har visats vara lokaliserade på samma platser på broskytan, vilket tyder på att de associerar med varandra. På egen hand var lubricins smörjande förmåga av PMMA, våra hydrofoba modellytor, dålig. Emellertid, om COMP först adsorberades på PMMA och sedan lubricin tillsattes uppmättes en låg friktionskoefficient (≈ 0.03). I det här fallet består synergin av att COMP möjliggör en stark inbindning till ytan av lubricin i konformationer som ger god smörjande förmåga. / <p>QC 20141202</p> / Stiftelsen för strategisk forskning - SSF

Předkládaná diplomová práce se zabývá extrakcí nanočástic oxidu titaničitého z produktů osobní péče, konkrétně opalovacích krémů a následnou charakterizací těchto částic. Počet komerčně dostupných produktů s obsahem nanočástic TiO2 se neustále zvyšuje a to se sebou přináší potřebu vyhodnotit potenciální osud a nepřímou expozici TiO2 nanošástic o různých velikostí a tvarů a zkoumat jejich celý životní cyklus. Bylo zkoumáno použití ultrafiltrace a ultracentrifugace jako extrakční metody. Dvě metody pro extrakci TiO2 nanočástic byly vyvinuty a aplikovány na vzorky opalovacích krémů. Extrahované částice mohou být použity pro ekotoxikologické studie, případně experimenty v mesokosmu. Velikost částic byla stanovena pomocí metody dynamického rozptylu světla a transmisní elektronové mikroskopie.

La complexité des membranes biologiques est à l'origine du développement des modèles membranaires artificiels comme outils indispensables à la compréhension des mécanismes d'interaction entre médicaments et membrane cellulaire. Cette thèse porte sur l'étude des interactions non spécifiques et spécifiques entre de nouvelles porphyrines glycoconjuguées utilisables en thérapie photodynamique (PDT) et des modèles membranaires biomimétiques (monocouches, bicouches planes supportées et liposomes) du rétinoblastome portant à leur surface une lectine spécifique du mannose. Les principales techniques utilisées pour cette étude sont la tensiométrie de surface, la spectrométrie de fluorescence, la microbalance à cristal de quartz avec mesure de dissipation (QCM-D) et diffusion quasi-élastique de lumière (DLS). Les porphyrines glycoconjuguées se sont avérées comme des molécules prometteuses, capables à interagir d'une manière non spécifique (pénétration passive) et spécifique (ciblage des récepteurs de type lectinique) avec les modèles membranaires du rétinoblastome.