A resina acrílica para base de próteses removíveis é capaz de aderir Candida spp. sobre sua superfície, possibilitando o aparecimento das estomatites protéticas. Um fator importante para essa aderência é a hidrofobicidade do polímero. Assim, a adição de radicais hidrofílicos à resina acrílica tem potencial de torná-la menos suscetível à formação de biofilmes, e merece ser investigado. O objetivo deste projeto foi avaliar os efeitos da copolimerização do ácido metacrílico sobre aderência microbiana e propriedades físicas em um material à base de polimetil metacrilato para base de próteses removíveis. Para os ensaios com a resina acrílica, espécimes de diferentes formatos foram divididos em grupos, conforme a concentração do ácido metacrílico, em volume, na porção líquida da resina (A: 0%; B: 10%; C: 20%, D:50%). A aderência de Candida albicans foi avaliada por meio da contagem de unidades formadoras de colônia (UFC) aderidas sobre os espécimes mantidos em caldo de cultura. Também foi estudadas a dureza Vickers, a resistência flexural, a rugosidade e a estabilidade de cor. Os grupos foram descritos por média ± desvios padrão e comparados, dentro de cada variável, por meio de ANOVA, com α = 0,05. No caso da aderência de C. albicans, transformação em log10 foi realizada antes da análise. Como resultado desse estudo, não foi possível observar diferenças na aderência de C. albicans com a adição do ácido metacrílico à resina acrílica (A: 5,0 ± 0.4, B: 5,0 ± 0.4, C: 5.2 ± 0.6 e D: 5.2 ± 0.3 log10(UFC)). Redução significante foi encontrada para os valores de dureza, onde os valores (em VHN) foram A: 19,0 ± 1,4A, B: 19,6 ± 1,3A, C: 19,6 ± 0,9A e D: 14,2 ± 0,6B. Não houve diferença significante para o teste de resistência flexural (A: 96,32 ± 8,25, B: 97,65 ± 6,11, C: 102,43 ± 8,61 e D: 106,34 ± 13,69 MPa); no entanto foi observada redução na rugosidade superficial com o aumento da concentração do ácido (A: 0,26 ± 0,05A, B: 0,17 ± 0,01B, C: 0,18 ± 0,03B e D: 0,13 ± 0,03C µm). Conclui-se que a copolimerização do ácido metacrílico em resina para base protética proporcionou mudanças nas propriedades físicas do material, com melhora na rugosidade, porém menor dureza. A aderência de C. albicans não sofreu interferência; futuros testes com outras espécies e na presença de proteínas salivares devem ser realizados a fim de determinar se a adição do ácido realmente possui potencial clínico. / Acrylic resins for denture base play an important role as reservoirs of micro-organisms, by increasing the risk of Candida ssp. colonization which is implicated in the pathogenesis of associated stomatitis. An important factor for this adherence is the polymer hydrophobicity. Thus, incorporation of polar radicals in the polymer could increase its hydrophylia, reducing this adherence. The main purpose of the present study was to investigate the antifungal activity of a denture base resin incorporating the methacrylic acid (MA) against Candida albicans by the counting of adherent cells and its effect on hardness, roughness and flexural strength of the material. 32 circular (14x4mm), 40 rectangular (65x10x3.3mm) and 40 square-shaped (10x10x3mm) specimens were divided into four groups, according to the concentration of MA substituted into the monomer component of a heat-polymerized acrylic resin (Lucitone 550), as follows: 0% (Control), 10%, 20% and 50% (v/v). Hardness was assessed by a hardness tester equipped with a Vickers diamond penetrator. A surface roughness tester was used to measure the surface roughness of the specimens, and a flexural strength testing was carried out on a universal testing machine. Variables were analyzed by ANOVA/Tukey\'s test (α=.05). Colonies were counted for each plated specimen and the colony-forming units per milliliter (CFU/mL) were then calculated. CFU/mL values for each concentration were compared by means of ANOVA/Tukey test after logarithmic (log 10) transformation (α=.05). A significant difference was found for hardness values (19.0±1.4A, 19.6±1.3A, 19.6±0.9A, 14.2±0.6B) VHN. Surface roughness values decreased with MA concentration increase (0.26±0.05A, 0.17±0.01AB, 0.18±0.03AB, 0.13±0.03B µm). No significant difference was found for flexural strengh (96.3±8.3A, 97.7±6.1A, 102.4±8.6A, 106.3±13.7A MPa) and among the four groups for the adherence assay (A: 5,0 ± 0.4, B: 5,0 ± 0.4, C: 5.2 ± 0.6 e D: 5.2 ± 0.3 log10 (CFU). For the tested acrylic resin, the addition of MA in the concentration of 50% reduced its hardness. Thus, the presence of MA around this concentration inside the monomer may compromise the tested material structure. Although MA didnt lower the flexural strength, regardless of the concentration, the values for surface roughness reduced as MA concentration increased, suggesting that MA addition may improve the acrylic resin texture, leading to less biofilm accumulation. The adherence of C. albicans was not influenced by the presence of MA. Future tests with other microorganisms and salivary proteins should be carried out to determine if this incorporation has a clinical potencial to be used.

A resina acrílica para base de próteses removíveis é capaz de aderir Candida spp. sobre sua superfície, possibilitando o aparecimento das estomatites protéticas. Um fator importante para essa aderência é a hidrofobicidade do polímero. Assim, a adição de radicais hidrofílicos à resina acrílica tem potencial de torná-la menos suscetível à formação de biofilmes, e merece ser investigado. O objetivo deste projeto foi avaliar os efeitos da copolimerização do ácido metacrílico sobre aderência microbiana e propriedades físicas em um material à base de polimetil metacrilato para base de próteses removíveis. Para os ensaios com a resina acrílica, espécimes de diferentes formatos foram divididos em grupos, conforme a concentração do ácido metacrílico, em volume, na porção líquida da resina (A: 0%; B: 10%; C: 20%, D:50%). A aderência de Candida albicans foi avaliada por meio da contagem de unidades formadoras de colônia (UFC) aderidas sobre os espécimes mantidos em caldo de cultura. Também foi estudadas a dureza Vickers, a resistência flexural, a rugosidade e a estabilidade de cor. Os grupos foram descritos por média ± desvios padrão e comparados, dentro de cada variável, por meio de ANOVA, com α = 0,05. No caso da aderência de C. albicans, transformação em log10 foi realizada antes da análise. Como resultado desse estudo, não foi possível observar diferenças na aderência de C. albicans com a adição do ácido metacrílico à resina acrílica (A: 5,0 ± 0.4, B: 5,0 ± 0.4, C: 5.2 ± 0.6 e D: 5.2 ± 0.3 log10(UFC)). Redução significante foi encontrada para os valores de dureza, onde os valores (em VHN) foram A: 19,0 ± 1,4A, B: 19,6 ± 1,3A, C: 19,6 ± 0,9A e D: 14,2 ± 0,6B. Não houve diferença significante para o teste de resistência flexural (A: 96,32 ± 8,25, B: 97,65 ± 6,11, C: 102,43 ± 8,61 e D: 106,34 ± 13,69 MPa); no entanto foi observada redução na rugosidade superficial com o aumento da concentração do ácido (A: 0,26 ± 0,05A, B: 0,17 ± 0,01B, C: 0,18 ± 0,03B e D: 0,13 ± 0,03C µm). Conclui-se que a copolimerização do ácido metacrílico em resina para base protética proporcionou mudanças nas propriedades físicas do material, com melhora na rugosidade, porém menor dureza. A aderência de C. albicans não sofreu interferência; futuros testes com outras espécies e na presença de proteínas salivares devem ser realizados a fim de determinar se a adição do ácido realmente possui potencial clínico. / Acrylic resins for denture base play an important role as reservoirs of micro-organisms, by increasing the risk of Candida ssp. colonization which is implicated in the pathogenesis of associated stomatitis. An important factor for this adherence is the polymer hydrophobicity. Thus, incorporation of polar radicals in the polymer could increase its hydrophylia, reducing this adherence. The main purpose of the present study was to investigate the antifungal activity of a denture base resin incorporating the methacrylic acid (MA) against Candida albicans by the counting of adherent cells and its effect on hardness, roughness and flexural strength of the material. 32 circular (14x4mm), 40 rectangular (65x10x3.3mm) and 40 square-shaped (10x10x3mm) specimens were divided into four groups, according to the concentration of MA substituted into the monomer component of a heat-polymerized acrylic resin (Lucitone 550), as follows: 0% (Control), 10%, 20% and 50% (v/v). Hardness was assessed by a hardness tester equipped with a Vickers diamond penetrator. A surface roughness tester was used to measure the surface roughness of the specimens, and a flexural strength testing was carried out on a universal testing machine. Variables were analyzed by ANOVA/Tukey\'s test (α=.05). Colonies were counted for each plated specimen and the colony-forming units per milliliter (CFU/mL) were then calculated. CFU/mL values for each concentration were compared by means of ANOVA/Tukey test after logarithmic (log 10) transformation (α=.05). A significant difference was found for hardness values (19.0±1.4A, 19.6±1.3A, 19.6±0.9A, 14.2±0.6B) VHN. Surface roughness values decreased with MA concentration increase (0.26±0.05A, 0.17±0.01AB, 0.18±0.03AB, 0.13±0.03B µm). No significant difference was found for flexural strengh (96.3±8.3A, 97.7±6.1A, 102.4±8.6A, 106.3±13.7A MPa) and among the four groups for the adherence assay (A: 5,0 ± 0.4, B: 5,0 ± 0.4, C: 5.2 ± 0.6 e D: 5.2 ± 0.3 log10 (CFU). For the tested acrylic resin, the addition of MA in the concentration of 50% reduced its hardness. Thus, the presence of MA around this concentration inside the monomer may compromise the tested material structure. Although MA didnt lower the flexural strength, regardless of the concentration, the values for surface roughness reduced as MA concentration increased, suggesting that MA addition may improve the acrylic resin texture, leading to less biofilm accumulation. The adherence of C. albicans was not influenced by the presence of MA. Future tests with other microorganisms and salivary proteins should be carried out to determine if this incorporation has a clinical potencial to be used.

There has been growing interest in designing and development of suitable micro or nano drug delivery system with the ability to target site specifically and release the payload in a predetermined fashion. Recently a new type of system called polyelectrolyte microcapsules and thin films have been proposed and developed for applications such as, biomedical devices to micro sensing and drug delivery. Owing to its advantages of mild preparation conditions, multifunctionality, with programmable characteristics and to encapsulate large amount of materials, it has shown immense potential. In the present research, multilayer polyelectrolyte thin films composed of Poly(methacrylic acid) (PMA) and Poly (vinyl pyrrolidone) (PVP) were deposited on the flat substrates using layer by layer (LBL) technique. The film growth and its deconstruction under physiological conditions were characterized using UV Visible spectrophotometer and Scanning Electron Microscopy (SEM). Hollow microcapsules composed of PMA and PVP were also produced with the help of sacrificial silica template using the same LBL adsorption technique. After coating the desired number of PVP and PMA layers, the colloidal template was removed with a buffer system composed of Hydrofluoric acid (HF) and Ammonium fluoride (NH4F). The obtained capsules were characterized for its surface morphology using SEM and Atomic Force Microscopy (AFM). The hydrogen bonding in capsule formation was confirmed by Fourier Transform Infrared Spectroscopy (FTIR). Encapsulation and release with the microcapsules was carried out using Rifampicin (Antitubercular drug) as a model drug. The interaction of empty and drug loaded capsules with Mycobacterium Smegmatis cell line was investigated. It was found that the empty capsules did not affect the cell growth indicating their biocompatibility. Confocal microscopy studies with Doxorubicin (anticancer drug), which is a naturally fluorescent molecule, showed the drug is indeed encapsulated inside the hollow capsule. From the above studies, it was concluded that polyelectrolyte capsules have the potential to be used for delivering 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

Des polymères à base de méthacrylate de poly(oxyde d'éthylène) (PEOMA) avec des chaînes pendantes PEO (Mn = 300 ou 950 g mol-1) ou des copolymères de PEOMA300 et d'acide méthacrylique (AMA) ont été synthétisés par polymérisation radicalaire contrôlée par les nitroxydes en utilisant une alkoxyamine (BlocBuilder®) comme amorceur en présence de SG1 et d'une faible quantité de styrène. Les copolymères à base de PEOMA300 et d'AMA sont thermo- et pH-sensibles. Les deux types de macroalkoxyamines ont été utilisés pour amorcer la copolymérisation en émulsion du méthacrylate de n-butyle et du styrène et former, par auto-assemblage induit par la polymérisation, des particules composées de copolymères à blocs amphiphiles, en absence ou présence de particules de silice. En absence de silice, des particules stabilisées de façon stérique ou électrostérique ont été formées. La polymérisation présente les caractéristiques d'une polymérisation contrôlée avec néanmoins la formation d'une faible proportion de chaînes mortes. L'effet du pH, de la force ionique et de la nature ou de la concentration des macroalkoxyamines sur la cinétique de polymérisation et la morphologie des particules a été étudié, et des sphères, des vésicules ou des nanofibres ont été obtenues. Les macroalkoxyamines à base de PEO s'adsorbent sur la silice via la formation de liaisons hydrogène entre les chaînes PEO et les groupes silanol. La synthèse de copolymères à blocs en surface de la silice a conduit à la formation de particules hybrides de différentes morphologies (bonhomme de neige, multipodes, framboise, coeur-écorce, têtard, mille pattes) liées à la taille de la silice, au pH et à la nature du macroamorceur / Water-soluble brush-type polymers composed of poly(ethylene)oxide methacrylate (PEOMA) units with PEO side groups of various chain lengths (Mn = 300 and 950 g mol-1) or of PEOMA300 with methacrylic acid (MAA) were synthesized by nitroxide-mediated polymerization using an alkoxyamine initiator (BlocBuilder®) and SG1 nitroxide in the presence of a low amount of styrene. The PEOMA300-MAA based copolymers showed a dual temperature/pH response. The two series of macroalkoxyamines were used in aqueous emulsion copolymerization of nbutyl methacrylate and styrene leading to the formation of particles composed of amphiphilic block copolymers through polymerization-induced self-assembly, in both the absence and presence of silica. The experiments performed in the absence of silica particles resulted in the formation of sterically or electrosterically stabilized latexes. The polymerization exhibited all the features of a controlled system with however the presence of a small proportion of dead chains. The effect of pH value, ionic strength and type and concentration of the macroalkoxyamine initiator on polymerization kinetics and latex morphologies was investigated. Depending on the reaction conditions, spherical particles, vesicles or nanofibers were successfully prepared. The PEO-based macroalkoxyamines were shown to adsorb on the silica surface via hydrogen bond interaction between PEO and the silanol groups. This enabled block copolymers to be generated in situ on the silica surface leading to hybrid particles with snowman, raspberry, daisy, core-shell, “tadpole-” and “centipede-” like morphologies depending on the silica particle size, pH value and type of macroinitiator

Ces travaux décrivent la synthèse de nanoparticules stabilisées par des polyélectrolytes d’originesynthétique (poly(acide (méth)acrylique)) ou naturelle (alginate) par polymérisation radicalairecontrôlée (PRC) de type RAFT en émulsion. Ce procédé est basé sur l’utilisation d’un polymèrehydrophile obtenu par RAFT (macroRAFT) qui est réactivé dans l’eau pour la polymérisation d’unmonomère hydrophobe. Des copolymères à blocs amphiphiles sont ainsi générés et s’auto-assemblent in situ pour former des nanoparticules. Dans un premier temps, nous avons cherché à conduire l’ensemble du procédé en milieu aqueux. Des études ont ainsi été menées sur la polymérisation RAFTdans l’eau de l’acide acrylique et de l’acide méthacrylique. Des homopolymères bien définis ont été obtenus sur une large gamme de conditions, puis ont été utilisés comme macroRAFTs pour la polymérisation en émulsion de monomères hydrophobes. Des nanoparticules stables constituées de copolymères à blocs amphiphiles bien définis ont été produites. Il a été montré que le contrôle de la polymérisation et la nucléation dépendaient fortement du pH, mais qu’une bonne stabilité colloïdale était néanmoins observée dans tous les cas. Ce procédé "one-pot " a ensuite été extrapolé à la synthèse de particules stabilisées par des copolymères hydrophiles de N-acryloylmorpholine (NAM) et de macromonomères d’alginate. Des nano-objets aux morphologies variées ont été obtenus. Afin de mieux appréhender la formation de ces morphologies, un système modèle employant un copolymère hydrophile de NAM et de macromonomère de polyNAM obtenu par polymérisation RAFT a été étudiépour la polymérisation en émulsion du styrène. / This work describes the synthesis of nanoparticles stabilized by polyelectrolytes from synthetic(poly((meth)acrylic acid)) or natural (alginate) source by controlled free radical polymerization (CRP),namely RAFT, in emulsion. This process is based on the use of a hydrophilic polymer prepared by RAFT (i.e. macroRAFT) which is reactivated in water for the polymerization of a hydrophobic monomer. The formation of amphiphilic block copolymers which self-assemble in situ leads to the formation of nanoparticles. Firstly, we tried to perform the whole process in water. The RAFT polymerization of acrylic acid and methacrylic acid was studied in this context. Well-defined homopolymers were obtained under a large range of conditions, and further used as macroRAFTs in emulsion polymerization of hydrophobic monomers. Stable nanoparticles composed of well-defined amphiphilic block copolymers were produced. It was shown that the control of the polymerization and the nucleation were strongly dependent on the pH. Nevertheless, a good colloidal stability wasobserved in all cases. This “one-pot” process was then extrapolated to the synthesis of particles stabilized by hydrophilic copolymers of N-acryloylmorpholine (NAM) and alginate macromonomer. Nano-objects with various morphologies were obtained. In order to better understand the formation of these morphologies, a model system using a hydrophilic copolymer of NAM and a polyNAM macromonomer obtained by RAFT polymerization was studied in styrene emulsion polymerization.

Made available in DSpace on 2014-12-17T15:42:31Z (GMT). No. of bitstreams: 1 ClaudioLV.pdf: 1496908 bytes, checksum: 9da02c26d9351b21019488117fc27924 (MD5) Previous issue date: 2007-05-28 / Dispersions composed of polyelectrolyte complexes based on chitosan and poly(methacrylic acid), PMAA, were obtained by the dropping method and template polymerization. The effect of molecular weight of PMAA and ionic strength on the formation of chitosan/poly(methacrylic acid), CS/PMAA, complexes was evaluated using the dropping method. The increase in molecular weight of PMAA inhibited the formation of insoluble complexes, while the increase in ionic strength first favored the formation of the complex followed by inhibiting it at higher concentrations. The polyelectrolyte complexation was strongly dependent on macromolecular dimensions, both in terms of molecular weight and of coil expansion/contraction driven by polyelectrolyte effect. The resultant particles from dropping method and template polymerization were characterized as having regions with different charge densities: chitosan predominating in the core and poly(methacrylic acid) at the surface, the particles being negatively charged, as a consequence. Albumin was adsorbed on templatepolymerized CS/PMAA complexes (after crosslinking with glutardialdehyde) and pH was controlled in order to obtain two conditions: (i) adsorption of positively charged albumin, and (ii) adsorption of albumin at its isoelectric point. Adsorption isotherms and zeta potential measurements showed that albumin adsorption was controlled by hydrogen bonding/van der Waals interactions and that brushlike structures may enhance adsorption of albumin on these particles / Dispers?es formadas a partir de complexos polieletrol?ticos de quitosana e de poli(?cido metacr?lico), PMAA, foram obtidas tanto pelo m?todo de gotejamento, como pelo m?todo de polimeriza??o em molde. O efeito da massa molar do PMAA e da for?a i?nica na forma??o dos complexos de quitosana/poli(?cido metacr?lico), CS/PMAA, foi avaliado usando o m?todo de gotejamento. O aumento da massa molar do PMAA inibiu a forma??o dos complexos insol?veis, enquanto o aumento da for?a i?nica primeiramente favoreceu a forma??o dos complexos, depois a inibiu, em altas concentra??es de eletr?litos de baixa massa molar. A complexa??o dos polieletr?litos foi fortemente dependente das dimens?es macromoleculares, tanto em termos da massa molar quanto do efeito de expans?o/contra??o dos novelos, devido ao efeito polieletrol?tico. As part?culas resultantes tanto do m?todo de gotejamento, como da polimeriza??o em molde foram caracterizadas por apresentarem regi?es com diferentes densidades de carga: a quitosana predominantemente presente na regi?o central e o poli(?cido metacr?lico), na superf?cie, sendo, portanto, as part?culas carregadas negativamente. A albumina foi adsorvida nos complexos de CS/PMAA obtidos por polimeriza??o em molde (depois de sofrerem reticula??o covalente usando glutaralde?do) e o pH foi controlado a fim de se obter duas condi??es: (i) adsor??o de albumina carregada positivamente e (ii) adsor??o de albumina em seu ponto isoel?trico. As isotermas de adsor??o e as medidas de potencial zeta mostraram que a adsor??o da albumina foi controlada por liga??es de hidrog?nio/intera??es de van der Waals e que as estruturas em forma de escova puderam aumentar a adsor??o da albumina nessas part?culas