Thesis (MSc (Chemistry and Polymer Science))--Stellenbosch University, 2008. / Reversible addition fragmentation chain transfer (RAFT)-mediated polymerization has emerged as a versatile method for preparing polymers with control over molecular weight and polydispersity. Inherent in its mechanism is the retention of the chain transfer agent, the RAFT agent, at the polymer chain ends. Typically RAFT agents are made up of two parts, the so called R (leaving) and Z (thiocarbonyl thio, stabilizing) groups. These are retained as the a-and the w-end groups of the final polymer, respectively. RAFT polymerization offers a ready method for preparing polymers with well defined end functionalities. The a-end functionality can easily be built into the R group. The Z group, however, is thermally unstable and can impart color and smell to the polymer. Hence, two new methods for Z end group removal were introduced. Both methods take advantage of the facile reaction between thiocarbonyl thio compounds and radicals. By matching the functionalities of the R group (a-end group) with that of the end modified w-chain end, both methods offer an easy route to accessing telechelic functional polymers. End functional polymers have many important uses in industry and in the biomedical field. An alcohol functional xanthate RAFT agent was synthesized and successfully used to conduct the RAFT-mediated polymerization of N-vinylpyrrolidone (NVP). Characterization by NMR and MALDI ToF MS confirmed that a-hydroxyl-w-xanthate-functional PVP was easily produced. In the first end group modification method radicals were generated as in atom transfer radical addition (ATRA). A hydroxyl functional a-haloester was used as the ATRA initiator with a Cu catalyst system. The alkyl radical produced by this ATRA initiator then replaced the Z group giving a telechelic hydroxyl functional polymer. NMR analysis showed that the thiocarbonyl thio end group was completely removed. The hydroxyl functionality was quantified by derivatizing with trichloro acetyl isocyanate and subsequent analysis by NMR. MALDI ToF MS analysis, however, was inconclusive. In the second method the thiocarbonyl thio end group was removed by simply heating the polymer with hydrogen peroxide, thereby replacing the Z group with a hydroxyl end group at the w-chain end, giving a telechelic functional polymer. The telechelic hydroxyl functional polymer was subsequently crosslinked with a trifunctional isocyanate to make a PVP hydrogel. This confirmed that the end-modified polymer was indeed telechelic. The swelling kinetics of this hydrogel were determined in water at 37 oC.

Thesis (PhD (Chemistry and Polymer Science)--University of Stellenbosch, 2008. / Xanthate-mediated polymerization was investigated as a tool for the preparation of well-defined poly(N-vinylpyrrolidone) and copolymers of N-vinylpyrrolidone. Some results regarding the monomer vinyl acetate are included, mostly for comparison purposes. The structure of the leaving/reinitiating group of the xanthate mediating agent was tuned to match the monomer reactivity. This was achieved by studying the initialization behaviour of monomer-xanthate systems via in situ 1H-NMR spectroscopy. Additionally, the latter technique was valuable to identify side reactions affecting the monomer, xanthate and/or polymeric species. Subsequently, experimental conditions were defined, and used to optimize the level of control achieved during polymerization. Block copolymers were prepared from a xanthate end-functional poly(ethylene glycol) with both vinyl acetate and N-vinylpyrrolidone. Finally, the preparation of poly(N-vinylpyrrolidone) with a range of well-defined end groups was achieved via postpolymerization treatment of the xanthate end-functional polymerization product. 3 different routes were investigated, which lead to poly(N-vinylpyrrolidone) with 1) aldehyde or alcohol, 2) thiol or 3) unsaturated ω-chain-end functionality, in high yield, while the α-chain-end functionality is defined by the structure of the xanthate leaving group. The ω-aldehyde end-functional poly(N-vinylpyrrolidone) was successfully conjugated to the lysine residues of the model protein lysozyme via reductive amination. Particular attention was drawn to characterizing the polymerization products. NMR spectroscopy, liquid chromatographic and mass-spectroscopic techniques were used. The major achievements emerging from polymer analysis carried out in this study included the following: - a library of NMR chemical shifts for N-vinylpyrrolidone derivatives; - an estimation of the critical conditions for poly(N-vinylpyrrolidone) relevant for separation according to the polymer chain-ends; - conditions for the separation of block-copolymers comprising a poly(ethylene glycol) segment and a poly(N-vinylpyrrolidone) or poly(vinyl acetate) segment via liquid chromatography; - valuable results on matrix-assisted laser ionization-desorption time-of-flight mass spectroscopy (MALDI-ToF-MS) of poly(N-vinylpyrrolidone).

Functional water-soluble polymers find applications in a variety of fields including waste-water treatment, pharmaceuticals, cosmetics, drug delivery, and hygiene. Despite the increased demand for these products, understanding of their synthesis by free-radical aqueous-phase polymerization has lagged behind that of polymers produced in organic solvents. In this doctoral work, the free-radical batch and semibatch aqueous-phase polymerization of N-vinylpyrrolidone (NVP), N-vinylformamide (NVF), N-vinylimidazole (NVI) and quaternized vinylimidazole (QVI), as well as NVP polymerized in n-butanol, has been studied. Kinetic models are developed to describe monomer conversion and polymer molecular weight (MW) behaviour of these systems. The expressions developed from independent pulsed-laser studies for propagation (kp) and termination (kt) rate coefficients, including their variation with monomer concentration and conversion, are shown to provide an excellent description of aqueous-phase NVP polymerization. Polymerization of NVP in butanol and of NVF in water are well-represented by the base NVP model, with differences in polymerization rate and polymer MWs simply accounted for by the differences in kp for the systems, indicating that the kt behaviour must be quite similar. The NVI/QVI study demonstrates the importance of a pH-dependent degradative addition reaction to monomer for NVI, with polymerization behaviour identical to that of QVI for pH 1, an effect captured in the model developed to describe the system. The aqueous-phase copolymerization of NVP and NVF was also studied, and reactivity ratios were determined to be very close to unity. This information was combined with the kp and kt expressions used to describe NVP and NVF homopolymerizations, with no other additional parameters required to model the copolymerization rate, copolymer composition and copolymer MW. This result demonstrates that the improved homopolymerization knowledge of these water-soluble monomers can be easily extended to understand their behaviour in copolymerization. / Thesis (Ph.D, Chemical Engineering) -- Queen's University, 2011-12-21 16:05:14.904

Thesis (MSc)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: The combination of natural and synthetic polymers allow for the synthesis of advanced hybrid copolymers. These hybrid copolymers have applications in biomedical areas, one such area being in drug delivery systems (DDS). In this study, a modular approach was used to prepare amphiphilic block copolymers with the ability to self-assemble into three dimensional structures. Reversible addition-fragmentation chain transfer (RAFT) was the synthetic tool used to mediate the polymerization of N-vinylpyrrolidone. RAFT is a versatile method to prepare polymers with control over molecular weight and dispersity. A xanthate chain transfer agent (CTA) was used to obtain the hydrophilic poly(N-vinylpyrrolidone) (PVP) block. An aldehyde functionality could be introduced due to the lability of the xanthate moiety, the procedure of which was effectively optimized to produce quantitative conversion. A dixanthate CTA was synthesized to produce a PVP chain which after the modification reaction, resulted in a α,ω-telechelic polymer. A polypeptide was synthesized via the ring-opening polymerization of Ncarboxyanhydrides (ROP NCA). The living and controllable ROP of NCAs is a method which results in polypeptides, but without a well-defined amino acid order. Poly(γ- benzyl-L-glutamate) (PBLG) was synthesized with a narrow dispersity (Đ = 1.10 – 1.15) using conditions that promote the retention of a terminal primary amine. A protected cysteine functionality was introduced via the terminal amine PBLG chain-end, using peptide synthesis techniques. This resulted in the conjugation of the aldehyde functional PVP and the cysteine terminal PBLG using a covalent, non-reducible thiazolidine linkage. The deprotection of the cysteine, more specifically the deprotection of the thiol was a non-trivial procedure. The thiol protecting acetamidomethyl (Acm) group could not be cleaved using traditional methods, but instead a modified procedure was developed to effectively remove the Acm group while inhibiting hydrolysis of the benzyl esters. It was determined that the conjugation reaction could effectively proceed in N,Ndimethylformamide (DMF) at a slightly elevated temperature and so continued to prepare the amphiphilic hybrid block copolymers, PVP-b-PBLG. A structurally different PBLG chain, namely PBLG-b-Cys was conjugated to the ω-aldehyde PVP and the conjugation efficiency was compared to our PBLG-Cys block. In the case of PBLG-b- Cys the in situ deprotection and conjugation as well as a two-step deprotection and conjugation reaction with PVP resulted in very low conjugation efficiency. The cysteine end-functional PBLG resulted in near quantitative conjugation with PVP. The critical micelle concentration (CMC) for PVP90-b-PBLG54 was determined to be 6 μg/mL, using fluorescence spectroscopy. Particle sizes were determined with TEM and DLS and found to range from 25 nm to 120 nm depending on the polymer block lengths as well as hydrophobic/hydrophilic block length ratios. Furthermore, when the micelles were subjected to an increased acidic environment, the labile benzyl ester bonds were hydrolyzed. This was observed with TEM where the particle sizes increased 10-fold to form vesicular structures. Hydrolysis was further confirmed with ATR-FTIR and 1H-NMR spectroscopy. Cytotoxicity tests confirmed that the copolymer micelles had good cell compatibility at high concentrations such as 0.9 mg/mL. Investigation into drug loading using a pyrene probe confirmed the viability of using PVP-b-PBLG as a responsive DDS. / AFRIKAANSE OPSOMMING: Die kombinasie van natuurlike en sintetiese polimere maak dit moontlik vir die sintese van gevorderde hibried kopolimere. Hierdie kopolimere het aanwending in biomediese gebiede, een so 'n gebied is in medisinale vervoer sisteme (MVS). 'n Modulêre benadering is in hierdie studie gebruik om amfifiliese blok kopolimere te berei. Omkeerbare addisie-fragmentasie kettingoordrag (OAFO) is gebruik as die sintetiese tegniek vir die polimerisasie van N-vinielpirolidoon (NVP). OAFO is 'n veelsydige metode om polimere te berei met beheer oor molekulêre gewig en dispersiteit (Đ). 'n Xantaat kettingoordrag agent (KOA) is gebruik om die hidrofiliese poli(N-vinielpirolidoon) (PVP) blok te sintetiseer. ‘n Aldehied endgroep was deur die terminale xantaat funksionaliteit berei, ‘n proses wat geoptimiseer is tot kwantitatiewe omsetting. 'n Di-xantaat KOA is gesintetiseer om, na modifikasie, 'n α, ω-telecheliese polimeer te produseer. Die polipeptied was gesintetiseer deur middel van ’n ringopening polimerisasie van Nkarboksianhidriede (ROP NKA). Die lewende en beheerbare ROP van NKAe is 'n metode wat lei tot polipeptiede sonder ’n gedefinieerde aminosuur volgorde. Poli(γ- benzyl-L-glutamaat) met 'n lae dispersiteit (Đ = 1.10 – 1.15), is gesintetiseer deur gebruik te maak van kondisies wat die behoud van 'n terminale primêre amien bevorder. 'n Beskermde sistien-funksionaliteit is ingebou via die terminale amien met behulp van peptiedsintese tegnieke. Die tiol beskerming van die asetamidometiel (Asm) groep kon nie gekleef word deur gebruik te maak van tradisionele metodes nie, maar ‘n nuwe proses is ontwikkel om die Asm groep te kleef sowel as om die hidrolise van die bensiel esters te inhibeer. Die koppelings reaksie het effektief verloop in DMF by 'n effens verhoogde temperatuur en sodoende is die amfifiliese hibried blok-kopolimere, PVP-b-PBLG berei. Twee verskillende PBLG kettings is gekoppel aan die ω-aldehied PVP en die koppeling doeltreffendheid is vergelyk. Daar is bevind dat net die sistien end-funksionele PBLG tot kwantitatiewe konjugasie kon lei. Die kritiese misel konsentrasie is bepaal vir PVP90-b-PBLG54 as 6 μg/mL met behulp van fluoressensie spektroskopie. Die deeltjie-groottes is bepaal met TEM en DLS en wissel van 25 nm tot 120 nm, afhangende van die polimeer bloklengtes sowel as hidrofobiese / hidrofiliese blok lengte verhoudings. Die miselle is blootgestel aan 'n verhoogde suur omgewing, wat tot die hidrolise van die bensiel ester groepe gelei het. TEM het getoon dat die deeltjie-groottes met 10-voud vergroot het tot vesikulêre strukture. Hidrolise is verder bevestig met ATR-FTIR en 1H-KMR spektroskopie. Sitotoksiese toetse het bevestig dat die miselle geen of min toksisiteit toon teenoor eukariotiese selle nie, selfs teen 'n hoë konsentrasies soos 0.9 mg/ml. Die medisinale behoud vermoë is met behulp van pireen bevestig en dus ook die potensiaal van PVP-b-PBLG as ‘n moontlike MVS.

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Il a été démontré que l’acidité de l’environnement tumoral jouait un rôle dans la résistance aux chimiothérapies. L’utilisation de nanovecteurs, tels que les nanocapsules lipidiques (LNC), permet non seulement d’améliorer le temps de biodistribution de substances actives, mais aussi de cibler l’environnement tumoral tout en protégeant les actifs de cet environnement acide. L’objectif de cette thèse porte ainsi sur l’optimisation et l’évaluation de LNC furtives et pH-sensibles dans le contexte du mélanome.Dans un premier temps, ces travaux ont consisté à caractériser la vascularisation de mélanomes humain et murin. Ces études ont permis de comparer différentes tumeurs (densité, taille et structure) et de déterminer si l’usage de nanomédecines est approprié dans ce contexte.La seconde partie s’est orientée sur l’élaboration de polymères combinant furtivité et pH-sensibilité. Ces copolymères composés de N-vinylpyrrolidone (NVP)et de vinylimidazole ont été synthétisés par polymérisation RAFT et post-insérés à la surface des LNC. Ces modifications ont donné lieu à des LNC présentant des charges de surface pH-dépendantes,entrainant une augmentation de leur internalisation à pH acide dans des cellules de mélanome. Finalement, des études de biodistribution ont mis en évidence l’intérêt de la NVP dans le développement de nanovecteurs furtifs. En conclusion, les copolymères développés ont permis de prolonger le temps de circulation, mais aussi d’apporter des propriétés pH-sensibles qui pourraient améliorer l’internalisation tumorale des LNC in vivo et donc de potentialiser l’effet d’une thérapie anticancéreuse. / Tumor acidity has been shown to play a major role in resistance to chemotherapy. The use of nanomedicines, as lipid nanocapsules (LNC), allows to protect drugs from this acidic environment. They can also improve the biodistribution of therapeutics and to target the tumor environment. The aim of this thesis concerns the evaluation and characterization of stealth and pH-sensitive LNC in the context of melanoma. Firstly, these works consisted in characterizing the vascularization of human and mice melanoma. These studies allowed to compare different tumors (density, size and structure), and determine if the used of nanocarrier is suitable in the context of melanoma.The second part of this thesis described the development and the characterization of new copolymers, combining stealth and pH-sensitive properties. These copolymers, composed of Nvinylpyrrolidone(NVP) and vinylimidazole, were synthesized by RAFT polymerization and were post in sertedonto LNC surface. These modifications allowed to obtain charge reversal nanocarriers, leading to increase their melanoma cell uptake underacid pH. Finally, biodistribution of these modified nanoparticles was studied in vivo and highlighted the interest of NVP in the development of stealth nanocarriers. To conclude, the developed copolymers able to extend nanocarrier circulation time and to provide pH-responsive properties which should increase the tumor internalization of LNC invivo and potentiate the effect of anticancer drugs.

Protein therapeutics offer numerous advantages over small molecule drugs and are rapidly becoming one of the most prominent classes of therapeutics. Unfortunately, they are delivered almost exclusively by injection due to biological obstacles preventing high bioavailability via the oral route. In this work, numerous approaches to overcoming these barriers are explored. PH-Responsive poly(itaconic acid-co-N-vinylpyrrolidone) (P(IA-co-NVP)) hydrogels were synthesized, and the effects of monomer ratios, crosslinking density, microparticle size, protein size, and loading conditions were systematically evaluated using in vitro tests. P(IA-co-NVP) hydrogels demonstrated up to 69% greater equilibrium swelling at neutral conditions than previously-studied poly(methacrylic acid-co-N-vinylpyrrolidone) hydrogels and a 10-fold improvement in time-sensitive swelling experiments. Furthermore, P(IA-co-NVP) hydrogel microparticles demonstrated up to a 2.7-fold improvement in delivery of salmon calcitonin (sCT) compared to methacrylic acid-based systems, with a formulation comprised of a 1:2 ratio of itaconic acid to N-vinylpyrrolidone demonstrating the greatest delivery capability. Vast improvement in delivery capability was achieved using reduced ionic strength conditions during drug loading. Use of a 1.50 mM PBS buffer during loading yielded an 83-fold improvement in delivery of sCT compared to a standard 150 mM buffer. With this improvement, a daily dose of sCT could be provided using P(IA-co-NVP) microparticles in one standard-sized gel capsule. P(IA-co-NVP) was also tested with larger proteins urokinase and Rituxan. Crosslinking density provided a facile method for tuning hydrogels to accommodate a wide range of protein sizes. The effects of protein PEGylation were also explored. PEGylated sCT displayed lower release from P(IA-co-NVP) microparticles, but displayed increased apparent permeability across a Caco-2 monolayer by two orders of magnitude. Therefore, PEG-containing systems could yield high bioavailability of orally delivered proteins. Finally, a modified SELEX protocol for cellular selection of transcellular transport-initiating aptamers was developed and used to identify aptamer sequences showing enhanced intestinal perfusion. Over three selection cycles, the selected aptamer library showed significant increases in absorption, and from an initial library of 1.1 trillion sequences, 5-10 sequences were selected that demonstrated up to 10-fold amplification compared to the naïve library. These sequences could provide a means of overcoming the significant final barrier of intestinal absorption. / text

<p>Degradable polymers have gained an increased attention in the field of biomedical applications over the past decades, for example in tissue engineering. One way of improving the biocompatibility of these polymers is by chemical surface modification, however the risk of degradation during the modification procedure is a limiting factor. In some biomedical applications, for example in nerve guides, a patterned surface is desired to improve the cell attachment and proliferation.</p><p>In this thesis a new non-destructive, single-step, and solvent free method for surface modification of degradable polymers is described. Poly(L-lactide) (PLLA) substrates have been functionalized with one of the following vinyl monomers; N-vinylpyrrolidone (VP), acrylamide (AAm), or maleic anhydride (MAH) grafts. The substrates were subjected to a vapor phase atmosphere constituted of a mixture of a vinyl monomer and a photoinitiator (benzophenone) in a closed chamber at very low pressure and under UV irradiation. Poly(ε-caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), and poly(trimethylene carbonate) (PTMC) have been surface modified with VP using the same procedure to show the versatility of the method. The wettability of all of the four substrates increased after grafting. The surface compositions were confirmed by ATR-FTIR and XPS. The VP grafted PLLA, PTMC and PLGA substrates have been shown to be good substrates for the normal human cells i.e. keratinocytes and fibroblasts, to adhere and proliferate on. The topography of substrates with well defined nano patterns was preserved during grafting, since the grafted layer is very thin. We have also shown that the method is useful for a simultaneous chemical and topographical modification of substrates by masked vapor phase grafting. The surface topography was determined with SEM and AFM.</p> / <p>Intresset för användningen av nedbrytbara polymerer till biomedicinska applikationer som till exempel vävnads rekonstruktion har ökat avsevärt de senaste decennierna. Ett sätt att öka biokompatibiliteten hos dessa polymerer är genom kemisk ytmodifiering, men risken för nedbrytning under själva modifieringen är en begränsande faktor. I vissa biomedicinska applikationer, till exempel nervguider, är det önskvärt att ha en väldefinierad ytstruktur för att öka vidhäftningen och tillväxten av celler.</p><p>I den här avhandlingen presenteras en ny ickeförstörande, lösningsmedelsfri enstegsprocess för ytmodifiering av nedbrytbara polymerer. Substrat av poly(L-laktid) (PLLA) har ytfunktionaliserats med var och en av följande vinylmonomerer, N-vinylpyrrolidon (VP), akrylamid (AAm) eller maleinsyraanhydrid (MAH). Substraten har exponerats för en gasfasatmosfär av en blandning av en vinylmonomer och en fotoinitiator (bensofenon) i en tillsluten reaktor vid mycket lågt tryck och under UV-strålning. Metodens mångsidighet har även påvisats genom att ytmodifiera substrat av poly(ε-kaprolakton) (PCL), poly(laktid-co-glykolid) (PLGA) och poly(trimetylen karbonat) (PTMC) med VP. Vätbarheten ökade för alla fyra materialen efter ympning med en vinylmonomer. Ytsammansättningen fastställdes med ATR-FTIR och XPS. De VP ympade filmerna av PLLA, PLGA och PTMC visade sig vara bra substrat för mänskliga celler, i detta fall keratinocyter och fibroblaster, att vidhäfta och växa på. Yttopografin hos filmer med väldefinierade nanomönstrade ytor kunde bevaras efter ympning, tack vare att det ympade lagret är så tunt. Gasfas metoden har också visat sig användbar för att simultant ytmodifiera både kemiskt och topografiskt genom maskad gasfasympning. Yttopografin bestämdes med SEM och AFM.</p>

Degradable polymers have gained an increased attention in the field of biomedical applications over the past decades, for example in tissue engineering. One way of improving the biocompatibility of these polymers is by chemical surface modification, however the risk of degradation during the modification procedure is a limiting factor. In some biomedical applications, for example in nerve guides, a patterned surface is desired to improve the cell attachment and proliferation. In this thesis a new non-destructive, single-step, and solvent free method for surface modification of degradable polymers is described. Poly(L-lactide) (PLLA) substrates have been functionalized with one of the following vinyl monomers; N-vinylpyrrolidone (VP), acrylamide (AAm), or maleic anhydride (MAH) grafts. The substrates were subjected to a vapor phase atmosphere constituted of a mixture of a vinyl monomer and a photoinitiator (benzophenone) in a closed chamber at very low pressure and under UV irradiation. Poly(ε-caprolactone) (PCL), poly(lactide-co-glycolide) (PLGA), and poly(trimethylene carbonate) (PTMC) have been surface modified with VP using the same procedure to show the versatility of the method. The wettability of all of the four substrates increased after grafting. The surface compositions were confirmed by ATR-FTIR and XPS. The VP grafted PLLA, PTMC and PLGA substrates have been shown to be good substrates for the normal human cells i.e. keratinocytes and fibroblasts, to adhere and proliferate on. The topography of substrates with well defined nano patterns was preserved during grafting, since the grafted layer is very thin. We have also shown that the method is useful for a simultaneous chemical and topographical modification of substrates by masked vapor phase grafting. The surface topography was determined with SEM and AFM. / Intresset för användningen av nedbrytbara polymerer till biomedicinska applikationer som till exempel vävnads rekonstruktion har ökat avsevärt de senaste decennierna. Ett sätt att öka biokompatibiliteten hos dessa polymerer är genom kemisk ytmodifiering, men risken för nedbrytning under själva modifieringen är en begränsande faktor. I vissa biomedicinska applikationer, till exempel nervguider, är det önskvärt att ha en väldefinierad ytstruktur för att öka vidhäftningen och tillväxten av celler. I den här avhandlingen presenteras en ny ickeförstörande, lösningsmedelsfri enstegsprocess för ytmodifiering av nedbrytbara polymerer. Substrat av poly(L-laktid) (PLLA) har ytfunktionaliserats med var och en av följande vinylmonomerer, N-vinylpyrrolidon (VP), akrylamid (AAm) eller maleinsyraanhydrid (MAH). Substraten har exponerats för en gasfasatmosfär av en blandning av en vinylmonomer och en fotoinitiator (bensofenon) i en tillsluten reaktor vid mycket lågt tryck och under UV-strålning. Metodens mångsidighet har även påvisats genom att ytmodifiera substrat av poly(ε-kaprolakton) (PCL), poly(laktid-co-glykolid) (PLGA) och poly(trimetylen karbonat) (PTMC) med VP. Vätbarheten ökade för alla fyra materialen efter ympning med en vinylmonomer. Ytsammansättningen fastställdes med ATR-FTIR och XPS. De VP ympade filmerna av PLLA, PLGA och PTMC visade sig vara bra substrat för mänskliga celler, i detta fall keratinocyter och fibroblaster, att vidhäfta och växa på. Yttopografin hos filmer med väldefinierade nanomönstrade ytor kunde bevaras efter ympning, tack vare att det ympade lagret är så tunt. Gasfas metoden har också visat sig användbar för att simultant ytmodifiera både kemiskt och topografiskt genom maskad gasfasympning. Yttopografin bestämdes med SEM och AFM. / QC 20101014