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

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.

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

Obtenção de insumo farmacêutico a partir das folhas de Cissampelos sympodialis Eichl e seu efeito sobre mediadores inflamatórios relevantes para a asma

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Dispersões sólidas de sinvastatina: preparação, caracterização, no estado sólido utilizando técnicas emergentes e estudo de estabilidade

This thesis aimed to assess the increase in solubility of simvastatin (SINV) with solid dispersions using techniques such as kneading (MA), co-solvent evaporation (ES), melting carrier (FC) and spray dryer (SD). Soluplus (SOL), PEG 6000 (PEG), PVP K-30 (PVP) e sodium lauryl sulphate (LSS) were used as carriers. The solid dispersions containing PEG [PEG-2(SD)], Soluplus [SOL-2(MA)] and sodium lauryl sulphate [LSS-2(ES)] were presented with a greater increase in solubility (5.02, 5.60 and 5.43 times respectively); analyses by ANOVA between the three groups did not present significant difference (p<0.05). In the phase solubility study, the calculation of the Gibbs free energy (ΔG) revealed that the spontaneity of solubilisation of SINV occurred in the order SOL>PEG >PVP 75%>LSS, always 80%. The phase diagrams of PEG and LSS presented solubilization stoichiometry of type 1:1 (type AL). The diagrams with PVP and SOL tend to 1:2 stoichiometry (type AL + AP). The stability coefficients (Ks) of the phase diagrams revealed that the most stable reactions occurred with LSS and PVP. The solid dispersions were characterized by Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), particle size distribution (PSD), near-infrared spectroscopy imaging (NIR-CI) and X-ray diffraction of the powder using the Topas software (PDRX-TOPAS). The solid dispersion PEG-2(SD) presented the greatest homogeneity and the lowest degree of crystallinity (18.2%). The accelerated stability study revealed that the solid dispersions are less stable than SINV, with PEG-2(SD) being the least stable, confirmed by FTIR and DSC. The analyses by PDRX-TOPAS revealed the amorphous character of the dispersions and the mechanism of increasing solubility

Trajetória dos assentamentos rurais financiados pelo crédito fundiário no estado do Rio Grande do Norte: uma análise da experiência do assentamento da fazenda Paz no município de Maxaranguape/RN

The market-assisted land reform (RAAM) has been constituted as an alternative of agrarian reform funded by the Programa Nacional do Crédito Fundiário (PNCF). It is a policy of acquisition, distribution and use of Earth ideologically disseminated and funded by the World Bank in the context of productive insertion of landless workers. Accordingly, this study seeks to analyze the trajectory of rural settlements financed by this policy, seeking to understand what factors promote or limit the process of rural development of those settlements. To do so, take as a reference case study of the Assentamento da Fazenda Paz, in the municipality of Maxaranguape in the State of Rio Grande do Norte. From the methodological point of view, bibliographical and documentary research were used, in addition to visits to the settlement and semi-structured interviews with the settlers, trade union leaders, consultants and technicians linked to the project. Assuming the reports of respondents, initially constructs the hypothesis that informal and formal institutions present in the Assentamento da Fazenda Paz were unable to effectively coordinate the actions of the agents. The results obtained showed the existence of a very complex undertaking, with a total area of 607 hectares and 80 families settled, endowed with good quality water and irrigation infrastructure, with assets of approximately R$ 5 million reais. Experience experienced by the settlers understood the development of complex systems of production and marketing of fruits and vegetables, with an emphasis on the cultivation of papaya in an area of 45 hectares based on modern irrigation system and extensive use of technology. Collective management of production, marketing, revenue and costs stood out as a major challenge for the settlers and their representative organisations, i.e. the Community Association and the cooperative. From this observation it was possible to identify two moments on the trajectory of the project: the first, between 2007-2011, considered by respondents as successful, in which the integration of public policies and abundant input of revenue from the commercialization of the fruits da Paz, mainly through the sale of papaya and pineapple in national and international markets, allowed an average remuneration of R$ 800.00 reais to R$ 1,000 reais seated/monthIn addition to the production of vegetables and other types of products for sale and consumption; the second, from 2012, characterized as a failure, due to the discontinuity of the cultivation, production and marketing of fruits based on the collective bargaining model deployed. Important factors explain the discontinuity of the project, including the model of agriculture implemented, difficulties related to the management of production, marketing and finance the venture, in addition to the breach of trust between the Board of the cooperative and the associates and the distancing of the governmental organizations more directly responsible for the project. It is therefore concluded that we must to rethink rural development as a multidimensional phenomenon, requiring a broad engagement between State and society under the foundations of a territorial development contract

Influência do envelhecimento acelerado na anatomia da testa de sementes de soja, cv. Monsoy 8400

Durante o processo de envelhecimento, as sementes sofrem alterações degenerativas que influenciam o seu potencial fisiológico. Entre estas alterações podem estar as modificações anatômicas nas camadas celulares da testa da semente. Objetivou-se, com este trabalho, verificar a relação entre a anatomia da testa de sementes de soja, cultivar Monsoy 8400 e a germinação, após o envelhecimento acelerado, pelo fato da testa apresentar um papel fundamental na conservação do potencial fisiológico das sementes. As sementes foram envelhecidas a 42ºC e 100% UR do ar por períodos de zero, 24, 48, 72 e 96 horas. Avaliaram-se os teores de água e a germinação, posteriormente à secagem, seções transversais da testa de 10 sementes de cada tratamento foram eletromicrografadas, com microscópio eletrônico de varredura,,observando-se as camadas das células paliçádicas, ampulhetas e parenquimáticas A germinação declinou com o aumento dos períodos de envelhecimento. Houve redução da espessura das camadas da testa nos períodos de 48, 72 e 96 horas deste processo. Observou-se que, principalmente, para os períodos de envelhecimento de 72 e 96 horas, que as células da camada hipodérmica apresentaram um aspecto de colapso, sendo este acentuado para o período de 96 horas. A redução da espessura das camadas sugere a ocorrência de um colapso das células que compõem tais camadas, sendo um fator causador da redução do potencial germinativo.

Germinação de sementes de alface submetidas a condicionamento osmótico durante o armazenamento

Em algumas espécies a técnica do condicionamento osmótico permite a obtenção de uma germinação rápida e uniforme. A pesquisa teve por objetivo verificar a eficiência do condicionamento osmótico de sementes de alface sobre a sua germinação. Sementes dos cultivares Mesa 659, Nabuco RS e Verônica, com dois níveis de viabilidade, foram submetidas ao condicionamento osmótico em solução (0,35 mol) de manitol por períodos de 3, 4, 5 e 6 dias sob 20ºC e em presença de luz. A seguir, as sementes foram submetidas à secagem (32ºC) por 12 horas em estufa com circulação de ar. As avaliações foram feitas pelo teste padrão de germinação aos 0, 10, 20, 30, 60 e 90 dias após o condicionamento e secagem das sementes. Utilizou-se o delineamento experimental inteiramente casualizado, com quatro repetições de 50 sementes, em esquema fatorial 2 × 5× 6, (dois níveis de vigor; cinco períodos de condicionamento osmótico e seis períodos de armazenamento após secagem). A resposta de sementes de alface ao condicionamento osmótico varia em função do cultivar e do período de condicionamento osmótico.

FITOTOXICIDADE DE FUNGICIDAS, ACARICIDAS E INSETICIDAS, SOBRE O MAMOEIRO (Carica papaya L.) CULTIVAR SUNRISE SOLO IMPROVED LINE 72/12 em CONDIÇÕES DE CAMPO

A presente pesquisa teve como objetivo estudar os efeitos fitotóxicos de fungicidas, acaricidas e inseticidas e algumas associações entre eles, em plantas de mamoeiros (Carica papaya L.) cv. Sunrise Solo Improved Line 72/12, em condições de campo, no município de São Mateus -- ES, pertencente à maior região produtora do Estado. O experimento foi arranjado em delineamento de blocos casualizados, com 4 repetições e 03 plantas úteis por parcela. Foram utilizados os seguintes produtos, com as respectivas doses, para cada 100 L de água: chlorothalonil (Daconil PM-200g); mancozeb (Dithane PM -- 200g); oxicloreto de cobre (Reconil -- 400g); thiabendazole (Tecto 450 -- 100ml); dicofol + tetradifon (Carbax -- 200ml); triazophós (Hostathion 400 BR -- 150ml); óxido de fenbutatina (Torque 500 SC -- 60ml); e abamectin (Vertimec 18 CE -- 50ml): Analisou-se a fitotoxicidade dos produtos testados, em relação à altura da planta, nº de folhas, número de flores e frutos ; diâmetro do caule e queimaduras ou injúrias foliares. As datas das avaliações foram: 01 dia antes das pulverizações, 15 dias e 30 dias após as mesmas. Os fungicidas Daconil BR, Reconil e Tecto 450; o fungicida acaricida Dithane PM; os acaricidas Carbax e Torque 500 SC; e o inseticida-acaricida Vertimec 18 CE, aplicados isoladamente, não afetaram o crescimento e a produção das plantas, nem causaram injúrias nas folhas das mesmas. A associação de fungicidas e fungicida-acaricida, com os acaricidas, ou inseticida-acaricida, não mostrou nenhum efeito fitotóxico sobre os parâmetros de crescimento avaliados, nem causaram queimaduras ou injúrias foliares.

Fitotoxicidade de fungicidas, acaricidas e inseticidas sobre o mamoeiro (Carica papaya L.) cultivar sunrise solo improved line 72/12

Estudaram-se os efeitos fitotóxicos de fungicidas, acaricidas e inseticidas e algumas associações entre eles, em plantas de mamoeiros (Carica papaya L.) cv. Sunrise Solo Improved Line 72/12, em condições de verão, no município de São Mateus - ES, localizado na região produtora do Estado. O experimento foi arranjado em delineamento de blocos casualizados, com 4 repetições e 03 plantas úteis por parcela experimental. Foram utilizados os seguintes produtos, com as respectivas doses, para cada 100 l de água: abamectin (Vertimec 18 CE - 50 ml); dicofol + tetradiphon (Carbax - 200 ml), fenbutatin oxide (Torque 500 SC - 60 ml); mancozeb (Dithane PM - 200g); oxicloreto de cobre (Reconil - 400g) e thiabendazole (Tecto 450 - 100ml). Analisou-se a fitotoxicidade dos produtos em relação à altura da planta, nº de folhas, número de flores e frutos ; diâmetro do caule e queimaduras ou injúrias foliares. As medições e contagens foram feitas um dia antes das pulverizações, 15 e 30 dias após. Constatou-se que o Vertimec 18 CE, associado ao Reconil ou ao Tecto 450, ocasionou leves injúrias foliares, detectadas aos 15 dias após as pulverizações, que se tornaram praticamente imperceptíveis, aos 30 dias após as pulverizações; e que Dithane PM, Reconil, Tecto 450, Carbax, Torque 500 SC, Dithane PM + Carbax, Dithane PM + Torque 500 SC, Dithane PM + Vertimec 18 CE, Reconil + Carbax, Reconil + Torque 500 SC, Tecto 450 + Carbax e, Tecto 450 + + Torque 500 SC não interferiram nos parâmetros de desenvolvimento e de produção estudados, bem como não causaram injúrias ou queimaduras nas folhas dos mamoeiros.

Conservação e qualidade de mangas 'Palmer' submetidas a tratamento com fungicidas e hidrotérmico

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