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

Estudo genético-clínico de mucopolissariodoses no estado do Ceará

As mucopolissacaridoses (MPS) são doenças genéticas raras decorrente da deficiência de enzimas lisossomais envolvidas no catabolismo de glicosaminoglicanos, resultando em um amplo espectro de manifestações clínicas, progressivas e multissistêmicas, exigindo tratamento por uma equipe multidisciplinar. Embora o Nordeste brasileiro seja uma região com grande taxa de consangüinidade e um efeito fundador envolvendo MPS, não há estudos caracterizando os pacientes dessa região. Nosso objetivo foi determinar o perfil epidemiológico, clínico e genético de casos não publicados com MPS provenientes do Ceará, identificando as diferenças entre outros estudos com MPS e possíveis problemas a serem enfrentados para a realização do diagnóstico precoce. O estudo foi seccional, descritivo, com amostra de pacientes com MPS em acompanhamento no Hospital Infantil Albert Sabin e Hospital Geral Cesar Cals no período de 2006-2013. Os dados foram obtidos a partir da avaliação clínica, revisão de prontuários médicos e entrevista com os pacientes e/ou familiares realizadas pelo investigador principal. Cinquenta e três pacientes foram incluídos no estudo (36 do sexo masculino), sendo 6 MPS I, 17 MPS II, 7 MPS III (3 MPSIII-A, 3 MPS III-B, 1 MPS III-C), 7 MPS IV-A, 16 de MPS VI. O óbito ocorreu em 16 casos (3 MPS I, MPS II 6, 1 MPS IIIA , IIIB 1MPS , 1 MPS IV , 4 MPS VI). A amostra foi composta principalmente por crianças. Houve elevada taxa de consangüinidade e recorrência familiar. Os tipos mais comuns foram MPS II e MPS VI. Exceto para macrossomia em MPS II, os dados de nascimento indicam que não houve risco para desenvolvimento de viii complicações perinatais. Os sintomas iniciaram em crianças com menos de 2 anos. As manifestações clínicas foram heterogêneas exceto para atraso no desenvolvimento neurológico em MPS III e manifestações esqueléticas em MPS IV. As principais características clínicas foram macrocefalia, baixa estatura, alterações odontológicas, respiratórias, cardíacas, hepatoesplenomegalia, hérnia umbilical, rigidez articular e anormalidades esqueléticas. A terapia de reposição enzimática foi instituída em 26 casos (4 MPS I, 10 MPS II, 12 MPS VI). Os problemas sócio-econômicos das famílias, o amplo espectro de sintomas e a gravidade da doença foram causas das dificuldades em realizar a avaliação periódica pela equipe multidisciplinar, além de exames complementares de maior custo para determinar as complicações da doença. Este foi o maior estudo transversal sobre MPS no Nordeste do Brasil. Em contraste com a maior incidência de MPS I na maioria das populações ocidentais, houve maior incidência de MPS II e VI. As alterações respiratórias foram um dos principais contribuintes para a mortalidade precoce, exceto nos casos de MPS I, em que a cardiomiopatia foi prevalente. A menor expectativa de vida ocorreu em MPS I. O envolvimento cognitivo foi comum em casos graves e o maior número de órgãos envolvidos representou maior risco de morrer. Para o diagnóstico precoce, deve-se buscar indivíduos afetados em famílias em que há parentes com MPS, além do maior reconhecimento de sinais e sintomas de MPS por profissionais de saúde

Monitoramento ambiental da costa do Rio Grande do Norte com base em sensoriamento remoto e geodésia de precisão

This paper presents models of parameters of Sea Surface Layer (SSL), such as chlorophyll-a, sea surface temperature (SST), Primary Productivity (PP) and Total Suspended Matter (TSM) for the region adjacent to the continental shelf of Rio Grande do Norte (RN), Brazil. Concentrations of these parameters measured in situ were compared in time quasi-synchronous with images AQUA-MODIS between the years 2003 to 2011. Determination coefficients between samples in situ and bands reflectance sensor AQUA-MODIS were representative. From that, concentrations of SSL parameters were acquired for the continental shelf of the RN (eastern and northern) analyzing the geographic distribution of variation of these parameters between the years 2009-2012. Geographical and seasonal variations mainly influenced by global climate phenomena such as El Niño and La Niña, were found through the analysis of AQUA-MODIS images by Principal Components Analysis (PCA). Images show qualitatively the variance and availability of TSM in the regions, as well as their relationship with coastal erosion hotspots, monitored along the coast of the RN. In one of the areas identified as being of limited availability of TSM, we developed a methodology for assessment and evaluation of Digital Elevation Models (DEM) of beach surfaces (emerged and submerged sections) from the integration of topographic and bathymetric data measured in situ and accurately georeferenced compatible to studies of geomorphology and coastal dynamics of short duration. The methodology consisted of surveys with GNSS positioning operated in cinematic relative mode involved in topographic and bathymetric executed in relation to the stations of the geodetic network of the study area, which provided geodetic link to the Brazilian Geodetic System (GBS), univocal , fixed, and relatively stable over time. In this study Ponta Negra Beach, Natal / RN, was identified as a region with low variance and availability of MPS in the region off, as characterized by intense human occupation and intense coastal erosion in recent decades, which presents potential of the proposed methodology for accuracy and productivity, and the progress achieved in relation to the classical methods of surveying beach profiles

Geoprocessamento de dados meteo-oceonográficos (cor do oceano e temperatura da superfície do mar) aplicado ao monitoramento ambiental na costa setentrional do Rio Grande do Norte

Orbital remote sensing has been used as a beneficial tool in improving the knowledge on oceanographic and hydrodynamic aspects in northern portion of the continental shelf of Rio Grande do Norte, offshore Potiguar Basin. Aspects such as geography, temporal and spatial resolution combined with a consistent methodology and provide a substantial economic advantage compared to traditional methods of in situ data collecting. Images of the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor onboard NASA's AQUA satellite were obtained to support systematic data collections related to the campaign of environmental monitoring and characterization of Potiguar Basin, held in May 2004. Images of Total Suspension Matter (TSM) and values of radiance standard were generated for the calculation of concentrations of total suspension matter (TSM), chlorophyll-a and sea surface temperature (SST). These data sets were used for statistical comparisons between measures in situ and satellite estimates looking validate algorithms or develop a comprehensive regional approach empirically. AQUA-MODIS images allowed the simultaneous comparison of two-dimensional water quality (total suspension matter), phytoplankton biomass (chlorophyll-a) variability and physical (temperature). For images of total suspension matter, the generated models showed a good correlation with the field data, allowing quantitative and qualitative analysis. The images of chlorophyll-a showed a consistent correlation with the in situ values of concentration. The algorithms adjusted for these images obtained a correlation coefficient fairly well with the data field in order that the sensor can be having an effect throughout the water column and not just the surface. This has led to a fit between the data of chlorophyll-the integration of the average sampling interval of the entire water column up to the level of the first optical depth, with the data generated from the images. This method resulted in higher values of chlorophyll concentration to greater depths, due to the fact that we are integrating more values of chlorophyll in the water column. Thus we can represent the biomass available in the water column. Images SST and SST measures in situ showed a mean difference DT (SST insitu - SST sat) around -0.14 ° C, considered low, making the results very good. The integration of total suspension matter, chlorophyll-a, the temperature of the sea surface (SST) and auxiliary data enabled the recognition of some of the main ways to fund the continental shelf. The main features highlighted were submerged canyons of rivers Apodi and Açu, some of the lines and beachrocks reefs, structural highs and the continental shelf break which occurs at depths around -60 m. The results confirmed the high potential for use of the AQUA-MODIS images to environmental monitoring of sea areas due to ease of detection of the field two-dimensional material in suspension on the sea surface, temperature and the concentration of chlorophyll-a