Non-invasive and controlled release of bioactive compounds is an important goal in the development of drug delivery systems and novel biomaterials for tissue engineering. This project aims to exert spatio-temporal control over the release of bioactive compounds from phospholipid vesicle carriers by crosslinking them with superparamagnetic iron oxide nanoparticles to form a magnetic release nanostructure. The magnetic properties of the nanoparticles allow release to be triggered by an alternating magnetic field (AMF), which induces localised heating and “melts” the vesicle membranes. The aggregates can also be manipulated in space by a static magnetic field to create patterned materials. Incorporation of these aggregates into hydrogels has created novel responsive biomaterials. Controlled release of ascorbic acid-2-phosphate has been used to induce collagen production by chondrocytes, demonstrating an AMF triggered cellular response in vitro. The existing system has been redesigned after detailed characterisation and assessment of the performance of each component. Magnetic release has been extensively assessed using fluorescence techniques to quantify release, and optimised through the development of new silica-derived nanoparticle coatings and aggregate formulations informed by quantitative characterisation of nanoparticle functionalisation. The replacement of calcium alginate hydrogels as a 3D cell culture matrix with hyaluronic acid- based hydrogels was found to eliminate gel-induced leakage of vesicle contents and also improves the compatibility of the system with a greater range of cell types. Recently the effective encapsulation and AMF-triggered release of proteins including enzymes has been demonstrated and released enzymes have been demonstrated to retain their activity. Released trypsin was shown to retain proteolytic activity while hyaluronidase released into hyaluronan-derived hydrogels has been demonstrated to influence the rheological properties of the gel. A galactose-terminated lipid has been synthesised that enables specific targeting of the asialoglycoprotein (ASGPR) cell surface receptor receptor found in human hepatocytes, demonstrating the potential for customisation of the MNPV system to particular requirements.

Tissue response to PNIPAM and HPC nanoparticles has been studied by implantation method. The results suggest that both PNIAPM and HPC nanoparticles possess good biocompatibility and they may serve as a good carrier for the applications of controlled delivery. Rheological properties of dispersions of IPN microgels composed of PNIPAM and PAAc have been studied. It is found that the IPN microgel dispersion can undergo a sol-gel transition at temperature above 33°C. In vivo drug release experiments suggest that the gelation procedure creates a diffusion barrier and thus leads to slow release. An emulsion method has been used to grow columnar crystals by mixing PNIPAM microgel dispersions with organic solvents. Effect of both temperature and microgel concentration on formation of columnar crystals has been studied. PNIPAM-co-NMA microgels have been used for the fabrication of crystalline hydrogel films by self-crosslinking microgels. The hydrogel film exhibits an iridescent. The thermally responsive properties and mechanical properties of this film have been studied. Melting temperature (Tm) of colloidal crystals self-assembled with PNIPAM-co-AAc microgels has been investigated as a function of pH, salt concentration and microgel concentration. It is revealed that Tm increases as pH value increases; Tm decreases with increase of salt concentration; Tm increases as microgel concentration increases. Phase behavior of PNIPAM-co-HEAc microgel dispersions has been investigated. It is observed that these microgel dispersions exhibit liquid, crystal, and glass phase. As microgel size increases, crystal phase shifts to low concentration range. As temperature increases, crystal phase shifts to high concentration ranges. These colloidal crystals can be stabilized by NaOH-induced gelation. Effect of NaOH concentration on formation of physical gelation has been investigated.

Orientador: Sandra Cristina dos Santos Rocha / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica / Made available in DSpace on 2018-08-03T15:25:48Z (GMT). No. of bitstreams: 1 Silva_OsvaldoSoaresda_D.pdf: 7702977 bytes, checksum: c2875b5b1fd2b063c810791c46fe4c58 (MD5) Previous issue date: 2003 / Resumo: o recobrimento de microgrânulos encontra suas principais aplicações nas indústrias de alimentos e farmacêutica. Os microgrânulos, segundo a tecnologia farmacêutica, são partículas com diâmetro na faixa de 0,1 a 0,8 mm, usados como excipiente para fabricação de comprimidos e cápsulas, no qual é inserido o princípio ativo do medicamento. Os principais objetivos do recobrimento de fármacos são: obter um produto com liberação controlada do princípio ativo; proteger os componentes; facilitar o manuseio e administração; mascarar sabor e isolar substâncias incompatíveis. A celulose microcristalina - MICROCEL é o principal excipiente usado na indústria farmacêutica, em formulações sólidas de dosagem oral, devido à baixa reatividade com os ingredientes ativos. Neste trabalho, estudou-se o recobrimento de MICROCEL com suspensão aquosa de Eudragit® em leito fluidizado. A suspensão polimérica à base de Eudragit® foi atomizada sobre o leito de partículas, através de um bico atomizador de duplo-fluido. As variáveis operacionais foram: pressão de atomização (Pat) igual a 68,95, 137,89 e 206,84 kPa; vazão de suspensão (Ws) igual a 6,4, 11,4 e 16,50 g/min; temperatura do ar na entrada do leito (Tar) igual a 50, 60 e 70°C e diâmetro de partícula (dp) igual a 0,200,0,269 e 0,329 mm. Os resultados experimentais permitiram investigar as variáveis-resposta: eficiência do processo, crescimento relativo de partículas, índice de aglomeração e razão tempo de atomização/tempo de processo, utilizando um planejamento fatorial 24. Os resultados principais observados foram: eficiência do processo de 61 a 92 %; crescimento de partículas de 10 a 13 %, índice de aglomerados de 0,02 a 4,70 % e razão de tempo de atomização/tempo de processo de 0,18 a 0,72. O planejamento experimental forneceu modelos estatisticamente significativos para as respostas eficiência do processo, crescimento de partículas e razão tempo de atomização/tempo de processo. A partir dos resultados do processo de recobrimento, considerou-se como faixa ótima de operação: P at = 137,89 kPa; Ws = 11,4 g/min; Tar = 70°C e dp = 0,269 mm. Nestas condições, realizaramse experimentos de recobrimento de um granulado de MICROCEL, impregnado com dic1ofenaco de sódio. Em seguida, o granulado recoberto foi submetido a um teste de dissolução do princípio ativo, em pH ácido e básico, para testar a gastro-resistência e validar o processo de recobrimento entérico / Abstract: Microgranules coating process has been applied mainly in both food and pharmaceutical industries. According to pharmaceutical technology, microgranules are particles of diameter range from 0.1 to 0.8 mm. The main objectives of solid partic1e coating are to obtain a product with controlled release of active components, to protect the partic1e from external conditions and to mask taste and odor. The objective of this work was to study the coating of MICROCEL (micro-crystalline cellulose) with an aqueous polymeric suspension of Eudragit® in a laboratory scale fluidized bed. The coating operation was carried out using a fluidized bed with top spraying by a double-fluid nozzle. In the present study, a 24 factor with three central points, 19 -run full factorial design was employed to evaluate the effects of the operational variables on the coating process The independent variables studied were the air pressure of atomization (P at); the flowrate of coating suspension (Ws), the inlet air temperature (Tar) and the particle diameter (dp) on the coating of MICROCEL. The values of the variables at the lower, central and upper levels were fixed in 68.95, 137.89 and 206.84 kPa for Pat; 6.4, 11.4 and 16.5 g/min for Ws; 50, 60 and 70°C for Tar and 0.200, 0.2ct9 and 0.329 mm for dp. The responses analyzed were the process efficiency, partic1es growth, agglomeration index and atomization-process time ratio. From the statistical analysis of the results, polynomial models for the response variables were adjusted. The results showed that process efficiency, partic1es growth and atomization-process time ratio could be accurately predicted over the range of experimental conditions. The results pointed out the optimized operational range for the coating process: Pat = 137.89 kPa; Ws = 11.4 g/min; Tar = 70°C and dp = 0.269 mm. For these conditions, experimental runs of coating of granulated MICROCEL and sodium diclofenac were carried out. The granulated mixture was prepared by wet granulation process. After that, tests were performed in a dissolution apparatus according to USP XXIV (American pharmacopeia). The tests had the objective of verifying the gastrointestinal resistance release and thus validate the coating process / Doutorado / Engenharia de Processos / Doutor em Engenharia Química

Orientador: Claudio Airoldi / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-26T11:26:42Z (GMT). No. of bitstreams: 1 Oliveira_CintiadosSantos_D.pdf: 3684874 bytes, checksum: 818c9e07a2f155ac52889f6ddcf9deab (MD5) Previous issue date: 2014 / Resumo: O biopolímero quitosana foi quimicamente modificado com aminas após a prévia proteção do grupo amino com benzaldeído. A reação de proteção forneceu o biopolímero BZL, que foi ativado com epicloridrina (EAC). A presença do grupo epóxido, proveniente da interação com a epicloridrina permitiu a inclusão de 2-aminometilpiridina, 2-aminopiridina, 4-aminopiridina, tetraetilenopentamina, 1,3-(aminopropilimidazol), 1-(2-aminoetil)piperazina e 1,4-bis(3-aminopropil) piperazina. Após a remoção do benzaldeído foram obtidos os biopolímeros CTN, C2MF, C4MF, TETF, IZLF, 2PPF e 3PPF, respectivamente, os quais foram caracterizados por análise elementar, difração de raios X, ressonância magnética nuclear do núcleo de carbono no estado sólido e espectroscopia na região do infravermelho. As caracterizações comprovaram o sucesso da reação de proteção dos grupos amino, bem como da remoção do benzaldeído. Os biopolímeros foram aplicados na remoção dos cátions metálicos cobre e cádmio, bem como na remoção dos corantes azul reativo 15 (RB-15), verde brilhante (BG), amarelo reativo (RY) e azul reativo (RB). Os experimentos foram realizados pelo método de batelada e os resultados obtidos foram ajustados à regressão não linear dos modelos de Langmuir, Freundlich e Sips, obtendo-se melhores ajustes ao último modelo. Os biopolímeros demonstraram uma melhor afinidade pelo cobre e dentre os corantes utilizados, uma melhor afinidade por RY. Os biopolímeros C2MF, C4MF, CTN, IZLF e TETF também foram carregados com os fármacos ibuprofenato de sódio (IBU) e diclofenaco de sódio (DCLO). Os estudos de liberação foram realizados em fluidos corpóreos simulados, obtendo-se perfis de liberação mais lentos para o DCLO. Através da calorimetria isotérmica foi investigado o processo de interação IBU ou Cu2+ com os biopolímeros. Os resultados indicaram processos endotérmicos, espontâneos e entropicamente favoráveis para o fármaco e exotérmicos, espontâneos e entalpicamente favoráveis para o cátion / Abstract: The chitosan biopolymer was chemically modified with amines after prior protection of the amino groups with benzaldehyde. The protection reaction provided the BZL biopolymer, which was activated with epichlorohydrin (EAC). The presence of epoxide groups derived from the epichlorohydrin allowed the inclusion of 2-aminomethylpyridine, 2-aminopyridine, 4-aminopyridine, tetraethylenepentamine, 1,3-(aminopropylimidazole), 1-(2-aminoethyl) piperazine and 1,4-bis(3-aminopropyl) piperazine. After bezaldehyde removal CTN, C2MF, C4MF, TETF, IZLF, 2PPF and 3PPF biopolymers were obtained, respectively, which were characterized by elemental analysis, X-ray diffraction, nuclear magnetic resonance of carbon nucleus in the solid state and infrared spectroscopy. The characterizations confirmed the success of protective reaction of amino groups as well as the benzaldehyde removal. The biopolymers were applied for the removal of copper and cadmium and also for reactive blue 15 (RB-15), brilliant green (BG), reactive yellow (RY) and reactive blue (RB) dyes. The experiments were carried out by batch method and the results were fitted with non-linear regression of the models of Langmuir, Freundlich and Sips, where the better fit was obtained using the last model. The biopolymers demonstrated better affinity for copper and among the dyes used, the best affinity was observed for RY. The C2MF, C4MF, CTN, TETF and IZLF biopolymers were also loaded with sodium ibuprofen (IBU) and diclofenac (DCLO) drugs. The release investigations were performed in simulated body fluids, resulting in slower release profile for DCLO. Through isothermal calorimetry processes, the interaction of IBU or Cu2+ with biopolymers was studied. The results indicated endothermic, spontaneous and entropically favorable processes for the drug and exothermic, spontaneous and favorable enthalpy process for the cation / Doutorado / Quimica Inorganica / Doutora em Ciências

Orientador: Fauze Ahmad Aouada / Resumo: Neste trabalho, primeiramente foram desenvolvidos hidrogéis nanocompósitos baseados em poli(ácido metacrílico) (PMAA) e nanoargilas cloisita-Na+, laponitas RD (Lpt RD) e RDS (Lpt RDS) por meio de polimerização via radical livre. A formação do nanocompósito e o grau de dispersão das nanoargilas junto a matriz polimérica foram investigados por análise de FTIR, MEV e DRX. A presença do argilomineral se apresentou um fator importante no que diz respeito ao aumento da capacidade de absorver água (Q) dos hidrogéis, atingindo um máximo em 5% de incorporação das Lpts no PMAA, além de uma melhora na estabilidade térmica dos nanocompósitos comprovada por TG. Assim como as nanocargas, o pH do meio também é um fator determinante para o controle do intumescimento. Pois, os grupos carboxílicos do PMAA sofrem ionização dependendo do pH da solução, aumentando assim o intumescimento do hidrogel. Segundo, foi realizado um estudo relativo à eficiência da adsorção pelos nanocompósitos (nanoargilas Lpt RD, Lpt RDS e cloisita-Na+) do herbicida paraquat (PQ) e sua posterior liberação em solução aquosa. Mais uma vez a presença do argilomineral se mostrou relevante, aumentando para 100% de eficiência no carregamento para nanocompósitos constituídos por 20% de nanoargilas. As adsorções em todas as formulações dos nanocompósitos se ajustaram à isoterma de Langmuir. Enquanto o modelo de isoterma de Freundlich foi o melhor modelo para a matriz sem nanoargila. Todas as isotermas apresentaram perfil de ads... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In this work, initially, nanocomposite hydrogels based on poly(methacrylic acid) (PMAA), closite-Na+, laponite RD (Lpt RD) and laponite RDS (Lpt RDS) nanoclays were synthesized from free radical polymerization. The formation of the nanocomposite and the degree of dispersion of the nanoclays into polymeric matrices were investigated by FTIR, SEM, and XRD techniques. The presence of the clay mineral was a significant factor because it increased the capacity of water absorption (SD) of the hydrogels, reaching a maximum of 5% of Lpts into PMAA. Besides, the thermal stability of the nanocomposites, confirmed by TG, was increased by clay presence. As the nanofillers, the pH of the environment is also a determinant factor for the control of swelling. Because the carboxyl groups of the PMAA undergo ionization depending on the pH of the solution, increasing the swelling of the hydrogel. Then, a study was carried out on the adsorption efficiency of the herbicide paraquat (PQ) using hydrogel nanocomposites (with Lpt RD, Lpt RDS, and cloisite-Na+ nanoclays) as adsorbent materials. After, its release properties were investigated in aqueous solution. The presence of nanoclay was again relevant, increasing to 100% its loading efficiency for nanocomposites made up of 20% nanoclays. Adsorption in all nanocomposite formulations fitted the Langmuir isotherm. Already, the paraquat sorption results followed the Freundlich isotherm model. All isotherms had favorable adsorption profiles, and it pre... (Complete abstract click electronic access below) / Doutor

Daily injections for basal insulin therapy are far from ideal resulting in hypo/hyperglycemic episodes associated with fatal complications in type-1 diabetes patients. The purpose of this study was to develop a thermosensitive copolymer-based in situ depot forming delivery system to provide controlled release of insulin for extended duration following a single subcutaneous injection, closely mimicking physiological basal insulin requirement. Size and nature of the incorporated therapeutic were observed to affect the release profile of insulin. Modification with zinc and chitosan preserved thermal, conformational, and chemical stability of insulin during the entire duration of storage (up to 9 months at 4 °C) and release (up to 3 months at 37 °C). In vivo, daily administration of long-acting insulin, glargine, resulted in fluctuating blood glucose levels between 91 – 443 mg/dL in type 1 diabetic rats. However, single administration of oleic acid-grafted-chitosan-zinc-insulin complexes incorporated in copolymer formulation demonstrated slow diffusion of insulin complexes maintaining peak-free basal insulin level of 21 mU/L for 91 days. Sustained release of basal insulin also correlated with efficient glycemic control (blood glucose <120 mg/dL), prevention of diabetic ketoacidosis and absence of cataract development, unlike other treatment groups. The suggested controlled basal insulin delivery system has the potential to significantly improve patient compliance by improving glycemic control and eliminating life-threatening diabetes complications. Furthermore, oleic acid-grafted-chitosan (CO) nanomicelles were investigated as a non-viral vector to deliver plasmid DNA encoding short hairpin RNA (shRNA) against pro-inflammatory cytokines to adipose tissue macrophages and adipocytes for the treatment of insulin resistance. Nanomicelles modified using mannose (COM) and adipose homing peptide (AHP) (COA) showed significantly higher uptake and transfection efficiency in inflamed macrophages- adipocytes co culture owing to glucose transporter-1 and prohibitin receptor mediated internalization, respectively. Ligand modified nanomicelles loaded with shRNA against tumor necrosis factor alpha (COM-TNFα) and monocyte chemoattractant protein-1 (COA-MCP1) demonstrated significant attenuation of pro-inflammatory cytokines and improved insulin sensitivity and glucose tolerance in obese-diabetic mice for six weeks post treatment with single dose of optimized formulation. Overall, chitosan nanomicelles mediated targeted gene therapy can help attenuate inflammation, the chief underlying cause of insulin resistance, thereby helping reverse the progression of diabetes. / National Institutes of Health (NIH) grant R15GM114701 / ND EPSCoR seed award FAR0030636

This diploma thesis is focused on development and characterization of hydrogel materials for agricultural use. In the experimental section, different methods of preparing these materials were designed and optimized according to previous literature review. In the characterization of resulting materials, the main attention was paid to the kinetics of swelling, to the solubility, the leaching of nitrate and of humic compounds. Thermogravimetric analysis represented another important characterization technique, which provided information about the content and form of water bound in the material. The development of the material aimed mainly at an agricultural application providing the delivery of nutrients to soil and regulation of water content in soil.

Orientador: Renato Grillo / Resumo: Inúmeros sistemas nanoestruturados vêm sendo desenvolvidos para o transporte e liberação modificada de defensivos agrícolas nos últimos anos. Tais sistemas vêm se mostrando uma potencial ferramenta para reduzir a toxicidade destes ingredientes ativos no ambiente, bem como vêm melhorando a eficiência de pesticidas no campo. Entretanto pouco se conhece sobre o destino, toxicidade e mecanismos de ação destes nanocarreadores no ambiente. Neste sentido, o objetivo do presente trabalho foi desenvolver potenciais sistemas de liberação modificada, encapsulando o herbicida atrazina (ATZ) em carreadores lipídicos nanoestruturados (CLNs) sem e contendo nanopartículas inorgânicas (magnéticas (Fe3O4@AO) e plasmônicas (Au@CTAB)), a fim de construir um sistema de liberação marcado que possa ser rastreado, auxiliando assim em futuras análises destes nanocarreadores no ambiente. Para o desenvolvimento das nanoformulações a técnica de emulsificação/evaporação solvente foi aplicada e diversos métodos físico-químicos foram empregados para a sua caracterização. As nanoformulações permaneceram estáveis por mais de 60 dias à temperatura ambiente. Além disso, os CLNs demostraram ter índice de polidispersão (PDI) < 0,2, potencial zeta entre -5,38 ± 0,27 a -23,5 ± 1,25 mV e uma eficiência de encapsulação maior que 90 % para a ATZ. As análises de microscopia eletrônica de varredura (MEV) revelaram ausência de agregados e morfologia esférica ao sistema. Além disso, as técnicas de espectroscopia de Infra... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Numerous nanostructured systems have been developed for the transportation and modified release of crop protection products in recent years. Such systems have been shown to be a potential tool to reduce the toxicity of these active ingredients in the environment, as well as improving the efficiency of pesticides in the field. However, little is known about the fate, toxicity and mechanisms of action of these nanocarriers in the environment. In this sense, the objective of the present work was to develop potential modified release systems, encapsulating the herbicide atrazine (ATZ) in nanostructured lipid carriers (CLNs) without and containing inorganic (magnetic (Fe3O4 @ AO) and plasma (Au @ CTAB)) nanoparticles) , in order to build a marked release system that can be tracked, thus assisting in future analyzes of these nanocarriers in the environment. For the development of nanoformulations, the solvent emulsification / evaporation technique was applied and several physical-chemical methods were used for its characterization. The nanoformulations remained stable for more than 60 days at room temperature. In addition, CLNs have been shown to have a polydispersity index (PDI) <0.2, zeta potential between -5.38 ± 0.27 to -23.5 ± 1.25 mV and an encapsulation efficiency greater than 90% for the ATZ. Scanning electron microscopy (SEM) analyzes revealed the absence of aggregates and spherical morphology to the system. In addition, Infrared spectroscopy (FTIR) and X-ray (DRX) techniq... (Complete abstract click electronic access below) / Mestre

<p>Astronaut diets on the International Space Station (ISS) depend on resupplied packaged food. However, missions to Mars of 3-5 years will not accommodate re-supply. In addition, many human macro and micronutrients degrade during long-term storage. Thus, growing nutritional plants aboard ISS is essential for providing astronauts with fresh, healthy produce. NASA is usingan experimental vegetable- production unit called VEGGIE to grow fresh salad crops aboard ISS to provide astronauts with healthy diets. VEGGIE is a small plant-growth chamber designed as a garden for astronauts that is low in mass and has a low power requirement. Veggie is equipped with light-emitting diodes (LEDs) but is exposed to the ISS cabin environment. Plants are grown with roots in a baked-ceramic substrate (arcillite) incorporating controlled-release fertilizer (Nutricote) and wicks delivering water by capillary action from a reservoir.</p><br><div>The fertilizerprills release nutrients into arcillite slowly over time. Different controlled-release types have the same amount of fertilizer but release it over different time periods. The Purdue Mitchell lab in collaboration with NASA is testing growth of salad crops within VEGGIE analogs under ISS-like environments in a growth chamber. Specifically, we are evaluating effects of different controlled-release fertilizer treatments as well as different substrate particle sizeson “cut-and-come-again” harvest scenarios, comparing productivity and quality of Lettuce as well as anAsian salad crop called Mizuna.<br></div><div><br></div><div>SS environments being mimicked include temperature: 24/21°C D/N, CO2: 2800 PPM D/N, RH: 45-50% D/N, and photoperiod: 16hours.Arcillitemedium contained one oftwo different fertilizer mixes: 7.5g18-6-8 T 70 + 7.5g 18-6-8 T100, or 7.5g18-6-8 T70 +7.5g 18-6-8 T180fertilizer/liter medium. LED Light treatment provides atotal PPFDof 330µmol m--2s-1 PAR; with 270µmol m--2s-1Red(R), 30µmol m--2s-1Blue (B), and 30µmol m--2s-1Green (G). Plants are grown under those conditions for 8 weeks, and harvested three times at 28, 42, and 56 days from planting. At each harvest, yield parameters as well as tissue mineral content have been measured for optimum fertilizer treatment selection.<br></div><div><br></div><div>Lettuce and Mizuna plants grown in a mix of 100% fine substrate particles (Profile) and fertilizer treatment of 50% T100:50%T70 had the higher yield as well as nitrogen contentcompared to those grown in 50%T180:50%T70. Growing mizuna plants in 100% profile resulted in higher shoot fresh weight; although no significant differences occurred for shoot dry weight. In addition, there was no significant interaction between substrate and fertilizer, which is reported by other research as one of the advantages of using controlled-release fertilizer<br></div>

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