Desenvolvimento de sistemas magnéticos com potencialidades terapêuticas para vetorização de fármacos

Magnetic targeting is being investigated as a means of local delivery of drugs, combining precision, minimal surgical intervention, and satisfactory concentration of the drug in the target region. In view of these advantages, it is a promising strategy for improving the pharmacological response. Magnetic particles are attracted by a magnetic field gradient, and drugs bound to them can be driven to their site of action by means of the selective application of magnetic field on the desired area. Helicobacter pylori is the commonest chronic bacterial infection. The treatment of choice has commonly been based upon a triple therapy combining two antibiotics and an anti-secretory agent. Furthermore, an extended-release profile is of utmost importance for these formulations. The aim of this work was to develop a magnetic system containing the antibiotic amoxicillin for oral magnetic drug targeting. First, magnetic particles were produced by coprecipitation of iron salts in alkaline medium. The second step was coating the particles and amoxicillin with Eudragit® S-100 by spray-drying technique. The system obtained demonstrated through the characterization studies carried out a possible oral drug delivery system, consisting in magnetite microparticles and amoxicillin, coated with a polymer acid resistant. This system can be used to deliver drugs to the stomach for treatment of infections in this organ. Another important finding in this work is that it opens new prospects to coat magnetic microparticles by the technique of spray-drying.

Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Anfotericina b pré-aquecida: um novo sistema terapêutico para infecções fúngicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Otimização de solução extrativa e desenvolvimento tecnológico de produto seco por aspersão de Psidium guajava L.

The increasing in the consumption of plant medicine by parts of the population generated a bigger need for studies. Drug substitutions, changes and adulterations at the production techniques are common places at plant-originated drugs trade, leading governmental departments of drug control round the world to adopt many analytical practices to medicinal plants. However, agronomic and technological issues cause characteristics and chemical composition variation at the drug, problem to be solved by the subject researchers. The present work aims to obtain a spray dried extract from a extractive solution obtained from Psidium guajava L. leaves based in book references that stress the intermediate dosage forms advantages. It also tries to validate useful methodologies for the quality control for both raw material and its derivates. Using eight sets of the spray dried extract (with Eudragit®, Aerosil ® e Avicel PH101 ® as drying adjuvants), the study proposes analytical methods using techniques commonly performed to plant medicines and its intermediate forms. As results, a viable spray-dried extract was obtained from a standartized extract solution. Among the studied adjuvants, the combination Aerosil ® with Eudragit ® showed the drying outcome, rheology, humidity and tannin content values that best fitted the demands of the Brazilian Pharmacopaea

Micropartículas poliméricas à base de xilana e Eudragit® S-100 contendo mesalazina visando à liberação cólon-específica

Colon-specific drug delivery systems have attracted increasing attention from the pharmaceutical industry due to their ability of treating intestinal bowel diseases (IBD), which represent a public health problem in several countries. In spite of being considered a quite effective molecule for the treatment of IBD, mesalazine (5-ASA) is rapidly absorbed in the upper gastrointestinal tract and its systemic absorption leads to risks of adverse effects. The aim of this work was to develop a microparticulate system based on xylan and Eudragit® S- 100 (ES100) for colon-specific delivery of 5-ASA and evaluate the interaction between the polymers present in the systems. Additionaly, the physicochemical and rheological properties of xylan were also evaluated. Initially, xylan was extracted from corn cobs and characterized regarding the yield and rheological properties. Afterwards, 10 formulations were prepared in different xylan and ES100 weight ratios by spray-drying the polymer solutions in 0.6N NaOH and phosphate buffer pH 7.4. In addition, 3 formulations consisting of xylan microcapsules were produced by interfacial cross-linking polymerization and coated by ES100 by means of spray-drying in different polymer weight ratios of xylan and ES100. The microparticles were characterized regarding yield, morphology, homogeneity, visual aspect, crystallinity and thermal behavior. The polymer interaction was investigated by infrared spectroscopy. The extracted xylan was presented as a very fine and yellowish powder, with mean particle size smaller than 40μm. Regarding the rheological properties of xylan, they demonstrated that this polymer has a poor flow, low density and high cohesiveness. The microparticles obtained were shown to be spherical and aggregates could not be observed. They were found to present amorphous structure and have a very high thermal stability. The yield varied according to the polymer ratios. Moreover, it was confirmed that the interaction between xylan and ES100 occurs only by means of physical aggregation

Metodologia para avaliação do tempo de cozimento e características tecnológicas associadas em diferentes cultivares de mandioca

O consumo culinário de raízes de mandioca é bastante generalizado em todo o mundo, sendo essa raiz amplamente utilizada na forma cozida, assada, frita ou integrando pratos mais complexos. O objetivo deste trabalho foi definir metodologia, avaliar o tempo de cozimento e algumas características associadas a este processo em 26 cultivares de mandiocas. Avaliaram-se os seguintes parâmetros avaliados foram cor da entrecasca; cor da polpa; dificuldade de soltar a entrecasca; dificuldade de palitar; porcentagem de água absorvida/perdida em relação ao peso dos toletes durante o processo de cozimento; cor dos toletes cozidos; formações de pontuações brancas no interior do tolete; formação de gel em volta dos toletes e tempo de cozimento observado para cozimento de 13 palitos. Ao final da avaliação concluiu-se que as melhores cultivares para utilização como mandioca de mesa foram a SRT-1105 (Mico), Milagrosa RG, Mantiqueira, IAC 522-30, IAC 576-70, sendo a última a que apresentou melhor resultado no teste de cozimento.

Produtividade de alface cv Lucy Brown influenciada por períodos de convivência com plantas infestantes e potencial alelopático da tiririca

This work was divided in two experiments, the first one to evaluate the lettuce productivity (cv Lucy Brown - American group) influenced by increasing and decreasing periods of coexisting with harmful plants, and a second moment, aiming at to evaluate the allelopathic potential of nutsedge (Cyperus rotundus L.) on the initial lettuce development.The experimental treatments constituted of six increasing and decreasing periods of coexisting with harmful plants, or control of it in the culture, considered from the plantation of the lettuce; being separate in two groups: Weeds and Clean weeds.In the second moment of the experiment, purple nutsedge aerial parts had been collected in the area of experiment 1, that drying had been after triturated and immersed in methylic alcohol P. A in ratios 10, 5,0 and 2.5% (w/ v) and later impregnated in germination paper, where had been placed lettuce seeds.The analyses of results, one concludes that the presence of C. rotundus plants can intervene with the germination, growth and development of the plants of lettuce cv Lucy Brown, and that initial periods of coexisting between the culture and the harmful are associate to an induction of the foliar area development, and can not express the reduction of productivity in the end of the cycle. Drawn out periods of competition induce the reduction of the lettuce foliar area, and then they will intervene with the yield productivity.

Caracterização morfológica de três genótipos de umezeiro selecionados como porta-enxertos para pessegueiro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Preparação e carcterização de complexos multicomponentes contendo ciclodextrinas e benznidazol

The benznidazole (BNZ) is the only alternative for Chagas disease treatment in Brazil. This drug has low solubility, which restricts its dissolution rate. Thus, the present work aimed to study the BNZ interactions in binary systems with beta cyclodextrin (β-CD) and hydroxypropyl-beta cyclodextrin (HP-β-CD), in order to increase the apparent aqueous solubility of drug. The influence of seven hydrophilic polymers, triethanolamine (TEA) and 1-methyl-2- pyrrolidone (NMP) in benznidazole apparent aqueous solubility, as well as the formation of inclusion complexes was also investigated. The interactions in solution were predicted and investigated using phase solubility diagram methodology, nuclear magnetic resonance of protons (RMN) and molecular modeling. Complexes were obtained in solid phase by spray drying and physicochemical characterization included the UV-Vis spectrophotometric spectroscopy in the infrared region, scanning electron microscopy, X-ray diffraction and dissolution drug test from the different systems. The increment on apparent aqueous solubility of drug was achieved with a linear type (AL) in presence of both cyclodextrins at different pH values. The hydrophilic polymers and 1-methyl-2-pyrrolidone contributes to the formation of inclusion complexes, while the triethanolamine decreased the complex stability constant (Kc). The log-linear model applied for solubility diagrams revealed that both triethanolamine and 1-methyl-2-pyrrolidone showed an action cosolvent (both solvents) and complexing (1-methyl-2-pyrrolidone). The best results were obtained with complexes involving 1-methyl-2-pyrrolidone and hydroxypropylbeta- cyclodextrin, with an increased of benznidazole solubility in 27.9 and 9.4 times, respectively. The complexes effectiveness was proven by dissolution tests, in which the ternary complexes and physical mixtures involving 1-methyl- 2-pyrrolidone and both cyclodextrins investigated showed better results, showing the potential use as novel pharmaceutical ingredient, that leads to increased benznidazole bioavailability

Produção, acúmulo e decomposição da serrapilhadeira e repartição da precipitação pluviométrica por espécies da caatinga

This study aimed to establish patterns of dynamics of litter and redistribution of rainfall of Caatinga vegetation. Sampling was done monthly for twenty three months in four areas: degraded, successional primary stage, secondary stage and late stage. We installed 72 collectors of 1.0 mx 1.0 m, with nylon fabric background in three areas. Litter deposited was fractionated into leaves, twigs, reproductive structures and miscellaneous, dried and weighed. To assess the stock of accumulated litter we used metal frame with dimensions of 0.5 mx 0.5 m, thrown randomly and collected monthly, taken to the laboratory for oven drying and weighed. To evaluate the decomposition, 40g of litter were placed in nylon bags (litterbags) mesh 1 mm ², dimensions 20.0 x 20.0 cm, being distributed on the soil surface and removed monthly, cleaned, dried and weighed. To evaluate the contribution of rainfall we used interceptometers installed 1.0 m above the ground surface, distributed under the canopy of six species of the caatinga, which evaluated the stemflow through collecting system installed around the stems of these species. The deposition of litter in the primary stage was 2.631,26 kg ha-1; 3.144,89 kg ha-1 in the secondary stage; 3.144,89 kg ha-1 in the late stage. The fraction of leaves was the largest contributor to the formation of litter in three stages. The degraded area showed greater accumulation of litter and decomposition has been sluggish during the dry period. We conclude that occurred greater litterfall in later stages. The late successional stage showed faster decomposition of litter, the evidence that is a better use of litter in nutrient cycling processes and incorporation of organic matter to the soil. The time required to decompose 50 % of the litter in the later stages of succession was lower indicating greater speed of release and reuse of nutrients by the vegetation. The specie jurema preta with less leaf area and consists of leaflets, showed greater internal precipitation in rain events of greater magnitude. The stemflow was not influenced by DAP and basal area. The water lost by trapping represented the largest proportion of total rainfall in all species studied

Viabilidade econômica, desempenho e características de carcaça de garrotes em confinamento alimentados com dietas contendo silagem de capins tanzânia ou marandu ou silagem de milho

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Distribuição do sistema radicular de porta-enxertos de umezeiro enxertados com o pessegueiro 'Aurora-1'

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Concentração de potássio na solução nutritiva e a qualidade e número de frutos de melão por planta em hidroponia

O experimento foi conduzido em hidroponia (NFT) no período de junho a novembro de 2001, na FCAV-UNESP em Jaboticabal-SP, situada a 21º15 22 Sul, 48º18 58 Oeste, e altitude de 575 metros. O híbrido Bônus n0 2 foi cultivado em blocos casualizados, em esquema de parcelas subdivididas, com seis repetições. Os elementos avaliados foram número de frutos por planta (2, 3, 4 e fixação livre) e concentração de potássio na solução nutritiva (66; 115,5; 165 e 247,5mg L-1). O experimento teve como objetivo avaliar a concentração de potássio na solução nutritiva e número de frutos por planta sobre a qualidade dos frutos do meloeiro. Concentrações maiores do que 66mg L-1 de potássio na solução nutritiva não promoveram incrementos nas características de qualidade dos frutos do meloeiro como: teor de sólidos solúveis médio de todos os frutos da planta, do segundo fruto, da acidez total titulável média de todos os frutos da planta, do primeiro fruto, do segundo fruto, do índice de maturação, da espessura da polpa e do índice de formato dos frutos. Frutos oriundos de plantas de melão com dois frutos apresentaram maior teor de sólidos solúveis e acidez total titulável, independente da concentração de potássio na solução nutritiva. O maior número de frutos por planta reduziu a espessura do mesocarpo dos frutos.

Pathogenicity of Metarhizium anisopliae for Ceratitis capitata (Wied.) (Diptera: Tephritidae) in soil with different pesticides

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Limites e possibilidades do programa nacional de alimentação escolar enquanto estratégia de promoção da segurança alimentar e nutricional no municipio de Macaíba/RN

This dissertation aims to understand the importance of the National School Feeding as a strategy for ensuring the promotion of food and nutrition security in the municipality of Macaíba / RN, taking into account the implementation of the Law School Feeding, 11,947, 2009. The program was extended to all public basic education, youth and adults, in addition to ensuring that 30% of transfers from FNDE, were intended for the purchase of products from family farms. The survey was conducted with 160 students from public schools and farmers nesting Quilombo dos Palmares II, who produce on their land vegetables, fruits and cereals for their own consumption, for sale in local markets, in addition to providing for PNAE. The reciprocity between neighbors, such as mutual aid and sharing of common goods was noticeable in this group of farmers, since it was necessary to meet weekly deliveries of products to schools. As students, we applied a test of acceptability in two schools located in rural and in urban areas, to learn the opinion of ourselves in relation to school food consumed. It was concluded that to be most effective program in the region, there must be a better match in school menus, so that it can be attractive to students and to ensure greater use of fresh food, the main ingredient of same, practice of nutrition education in schools, to teach students the importance of food to health. In relation to local management, noted the need for adjustments bureaucratic as hiring staff for the departments, in order to be more agile in releasing payments to farmers, in addition to hiring assistants general services for schools, one Since the cooks exert dual role, the cooking while being responsible for cleaning the entire school environment. Government investments in the rural sector would be extremely valuable for farmers, since they need financial resources to purchase inputs, irrigation projects for gardens, availability of land for planting, transportation to facilitate the delivery of its products to schools and technical assistance more frequently