Development of composite particles for pulmonary delivery

In this work, biocompatible and biodegradable poly(D-L-lactide-co-glycolide) (PLGA) microparticles with the potential for use as a controlled release system of vaccines and other drugs to the lung were manufactured using supercritical CO2, through the Supercritical Assisted Atomization (SAA) technique. After performing a controlled variance in production parameters (temperature, pressure, CO2/solution flow ratio) PLGA microparticles were characterized and later used to encapsulate active pharmaceutical ingredients (API). Bovine serum albumin (BSA) was chosen as model protein and vaccine, while sildenafil was the chosen drug to treat pulmonary artery hypertension and their effect on the particles characteristics was evaluated. All the produced formulations were characterized in relation to their morphology (Morphologi G3 and scanning electronic microscopy (SEM)), to their physical-chemical properties (X-ray diffraction (XRD, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR)) and aerodynamic performance using an in vitro aerosolization study – Andersen cascade impactor (ACI) - to obtain data such as the fine particle fraction (FPF) and the mass median aerodynamic diameter (MMAD). Furthermore, pharmacokinetic, biodegradability and biocompatibility tests were performed in order to verify the particle suitability for inhalation. The resulting particles showed aerodynamic diameters between the 3 and 5 μm, yields up to 58% and FPF percentages rounding the 30%. Taken as a whole, the produced microparticles do present the necessary requests to make them appropriate for pulmonary delivery.

Synthesis of Polymeric Nanoparticles for biomedical delivery applications

Polymeric nanoparticles (PNPs) have attracted considerable interest over the last few years due to their unique properties and behaviors provided by their small size. Such materials could be used in a wide range of applications such as diagnostics and drug delivery. Advantages of PNPs include controlled release, protection of drug molecules and its specific targeting, with concomitant increasing of the therapeutic index. In this work, novel sucrose and cholic acid based PNPs were prepared from different polymers, namely polyethylene glycol (PEG), poly(D,L-lactic-co-glycolic acid) (PLGA) and PLGA-co-PEG copolymer. In these PNP carriers, cholic acid will act as a drug incorporation site and the carbohydrate as targeting moiety. The uptake of nanoparticles into cells usually involves endocytotic processes, which depend primarily on their size and surface characteristics. These properties can be tuned by the nanoparticle preparation method. Therefore, the nanoprecipitation and the emulsion-solvent evaporation method were applied to prepare the PNPs. The influence of various parameters, such as concentration of the starting solution, evaporation method and solvent properties on the nanoparticle size, size distribution and morphology were studied. The PNPs were characterized by using atomic force microscopy (AFM), scanning electron microscopy (SEM) and dynamic light scattering (DLS) to assess their size distribution and morphology. The PNPs obtained by nanoprecipitation ranged in size between 90 nm and 130 nm with a very low polydispersity index (PDI < 0.3). On the other hand, the PNPs produced by the emulsion-solvent evaporation method revealed particle sizes around 300 nm with a high PDI value. More detailed information was found in AFM and SEM images, which demonstrated that all these PNPs were regularly spherical. ζ-potential measurements were satisfactory and evidenced the importance of sucrose moiety on the polymeric system, which was responsible for the obtained negative surface charge, providing colloidal stability. The results of this study show that sucrose and cholic acid based polymeric conjugates can be successfully used to prepare PNPs with tunable physicochemical characteristics. In addition, it provides novel information about the materials used and the methods applied. It is hoped that this work will be useful for the development of novel carbohydrate based nanoparticles for biomedical applications, specifically for targeted drug delivery.

Development of Chitosan and Poly (Vinyl Alcohol) Blended scaffolds for cell culture using supercritical fluids technology

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Mestrado Integrado em Engenharia Química e Bioquímica

Répartition des foraminifères benthiques dans les gisements de surface du Miocène d'Aquitaine (SW de la France)

The Aquitaine Basin (southwestern France) is known since long ago for its richness in marine miocene deposits of various facies. A few stratotypes concerning this period have been described in the investigated area. The stratigraphical framework has been recently revised and the study of new exposures completes our knowledge on these levels. In the present work, the authors produce a biostratigraphical distribution of about 160 species (larger and smaller foraminifera), found in the surface exposures of Aquitaine, from the topmost Oligocene (Chattian) through to Middle Miocene (including Serravallian). As a rule, the common species without significant ranges have not bcen mentioned. The microfaunas of several exposures have been thoroughly revised, which has allowed to precise the distribution of many species and induced a few modifications of the results previously produced. Synonymy problems and new taxonomical revisions have been taken into account. Of course, this work will be probably submitted to some changes according to new research on the already known exposures or other more recently discovered.

Etude de populations de Glycymeris (Bivalvia, Glycymerididae) du Miocène d'Aquitaine, Sud-Ouest de la France

Abundant crops of Glycymeris have been made in the neritic bioclastic deposits of the Aquitaine Basin. After an outline about the Chattian taxa, the 5 Lower Miocene lineages are presented; G. cor is plainly predominant. Then, the Middle Miocene faunas are also detaiIed, G. inflatus and G. bimaculatus being the most frequent taxa. A test of biometrical analysis about the G. cor species is presented.

Optimization of bioplastics production from cheese whey

Dissertation presented in partial fulfillment of the requirements for the degree of Master in Biotechnology

On international cost-sharing of pharmaceutical R&D

Ramsey pricing has been proposed in the pharmaceutical industry as a principle to price discriminate among markets while allowing to recover the (fixed) R&D cost. However, such analyses neglect the presence of insurance or the fund raising costs for most of drug reimbursement. By incorporating these new elements, we aim at providing some building blocks towards an economic theory incorporating Ramsey pricing and insurance coverage. We show how coinsurance affects the optimal prices to pay for the R&D investment. We also show that under certain conditions, there is no strategic incentive by governments to set coinsurance rates in order to shift the financial burden of R&D. This will have important implications to the application of Ramsey pricing principles to pharmaceutical products across countries.

Digital-domain self-calibration technique for video-rate pipeline A/D converters using Gaussian white noise

Electronics Letters Vol.38, nº 19

Problèmes posés par la population sporo-pollinique d'un niveau à plantes de la série de Buarcos (Portugal)

L'analyse pollinique des sédiments argileux, riches en macrorestes de végétaux, du "Belasien» (Crétacé inférieur) de Buarcos a permis reconnaître la présence d'une riche microflore. On a, nottament, reconnu la présence de: Concavisporites punctatus, Auritulinosporites complexis, Chomotriletes sp., Trilobosporites cf. bernissartensis, Apiculatisporites vulgaris, Cicatricosisporites sp. 1, Cicatricosisporites sp. 2. Cicatricosisporites sp. 3, Cicatricosisporites sp. 4, Cicatricosisporites sp. 5, Cicatricosisporites sp. 6. Costatoperforosporites fistulosus, Ceratosporites sp. l, C. cf. equalis, Ischyosporites teixeirae n. sp., Liburnisporites sp. AequitriraditeS cf. spinulosus, Cedripites lusitanicus, Clavatipollenites cf. hughesi. Après discution de la stratigraphie des diffèrentes espèces on sugère une âge barremo-aptien pour cette association malgré la présence de l'ensemble Apiculalisporites vulgaris-Classopollls major plutôt d'âge Aptien.

O Cristianismo no Japão e o Episcopado de D. Luís Cerqueira

Dissertação de doutoramento em História dos Descobrimentos e da Expansão Portuguesa

Difficultés d'adaptation de questionaire sur les transmissions entre famille et écoles en contextes linguistiques et culturels différents

Les résultats des études PISA – aussi bien en ce qui concerne celle de 2000 comme celle de 2003 - n’ont guêre été satisfaisants pour de nombreux pays de l’OCDE (ce n’est pas le cas pour la Belgique!). Par exemple Portugal, s’il présente des résultats comparables à la moyenne des pays européens ou même supérieurs pour la région de Lisbonne et la vallée du Tage, présente des résultats inférieurs pour l’ensemble du territoire. La Suisse est, curieusement, un autre pays qui se situe en deçà des expectatives. Selon le rapport 2003 (Ramalho, 2004 :50), les études comparatives en littéracie (lecture) et en numéracie n’ont pas démontré de différence significative par rapport aux résultats de 2000. Nous avons pris connaissance d’une étude suisse qui avait pris pour point de départ des résultats également défavorables, pour ce pays, au même rapport PISA : cette recherche analyse l’insertion socio-économique des familles comme également l’influence des transmissions familiales sur les parcours scolaires des élèves.

Télédetection en milieu périurbain. Détection et localisation du changement de l'occupation du sol par intégration des donnés-satellite SPOT HRV dans un système d'information géographique

Thèse pour obtenir le grade de DOCTEUR DE L' UNIVERSITÉ PARIS XII, Discipline: Urbanisme Aménagement

Social network analysis applied to knowledge creation and transfer in the portuguese agricultural R&D field: an exploratory study

Paper presented at the 9th European Conference on Knowledge Management, Southampton Solent University, Southampton, UK, 4-5 Sep. 2008. URL: http://academic-conferences.org/eckm/eckm2008/eckm08-home.htm

Gérer la distance: les sauts d'échelle dans les relations sociales

Espaces et sociétés, N.79, modes de vie et société portugaise, pág. 93-106