Coaxial electrospinning is a technique that allows the production of nanofibers with a core–shell structure. Such fibers present several advantages as materials for the preparation of scaffolds, namely due to the possibility of combining a core with the desired mechanical properties with a shell prepared from biocompatible materials that will establish proper interactions with the host. Herein, core-shell fibrous meshes, composed of a polycaprolactone (PCL) core and a functionalized gelatin shell, were prepared by coaxial electrospinning and then photocrosslinked under UV light aiming to be used in vascular tissue regeneration. The suitability of the meshes for the pretended biomedical application was evaluated by assessing their chemical/physical properties as well as their haemo and biocompatibility in vitro. The obtained results revealed that meshes’ shell prepared with a higher content of gelatin showed fibers with diameters presenting a unimodal distribution and a mean value of 600 nm. Moreover, those fibers with higher content of gelatin also displayed lower water contact angles, and therefore higher hydrophilicities. Such features are crucial for the good biologic performance displayed by these meshes, when in contact with blood and with Normal Human Dermal Fibroblasts cells.

In the present study, small-sized porous scaffolds were obtained from the freeze-drying of sodium hyaluronate/chitosan polyelectrolyte complexes. The obtained materials were characterized by a set of techniques including attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, swelling determination and weight loss studies. The morphology of the scaffolds was observed using scanning electron microscopy. Thermal characterization ofthe scaffolds was also performed by dynamic mechanical thermal analysis and thermogravimetric analysis. Finally, the cytotoxic profile of the prepared scaffolds was evaluated in vitro, using mesenchymal stem cells. The results obtained showed that cells adhered to scaffolds and proliferated. This study also confirmed that the degradation by-products of sodium hyaluronate/chitosan scaffold are noncytotoxic, which is fundamental for its application in the biomedical field.

In this work, porous scaffolds obtained from the freeze-drying of pectin/chitosan polyelectrolyte complexes were prepared and characterized by FTIR, SEM and weight loss studies. Additionally, the cytotoxicity of the prepared scaffolds was evaluated in vitro, using human osteoblast cells. The results obtained showed that cells adhered to scaffolds and proliferated. The study also confirmed that the degradation by-products of pectin/chitosan scaffold are noncytotoxic.

Edible films are promising carriers for probiotics and can be composed by agrifood residues, which are usually rich in polymers and bioactive compounds. In this work, starch-based films were enriched with three types of agrifood residues (quince, potato and orange peels) and the incorporation of the probiotic Lactobacillus rhamnosus was studied, as well as the addition of inulin as a protective prebiotic. The resulting films were characterized in terms of mechanical properties, physicochemical properties, lactobacilli viability and microbiological properties. The mechanical properties of the films generally decreased with the introduction of L. rhamnosus, although this was highly dependent on the film composition. All films exhibited water vapor permeabilities in the typical range of starch-based films and were not greatly affected by the inclusion of probiotics. The loss of probiotic viability during films production was strongly related to the pH of the film-forming solutions. Films with agrifood residues had a slower loss of probiotic viability during storage, when compared to plain starch films, which may be explained by the presence of antioxidant compounds. Inulin was expected to improve viability, but this was not observed. Microbiological analysis showed that agrifood residues powders contained natural contaminant bacteria that were partially eliminated during film formation. Moreover, none of the target foodborne pathogens were detected in the analyzed samples. Overall, the results suggest that edible films containing agrifood residues can be a promising material for the delivery of probiotics and/or as primary packaging for some food products.

The solubility of diflunisal, a nonsteroidal anti-inflammatory drug (NSAID), in supercritical carbon dioxide (scCO2) was measured at (308.2, 318.2, and 328.2) K and in the pressure range from (9.0 up to 25.0) MPa. Results were obtained using a static analytical method. Experimental solubility was found to be between 0.54·10−6 and 8.07·10−6 (in terms of diflunisal mole fraction). Experimental data were satisfactorily correlated with an equation-of-state (EOS) model: the Peng−Robinson cubic equation of state (PR−EOS) together with the conventional van der Waals mixing and combining rules. Solid properties were estimated by different methods available in the literature. The solubilities of several NSAIDs in SCFs, namely in scCO2, were obtained from the literature and plotted and represented as a function of the corresponding sublimation pressures and fusion temperatures.

The measurement and correlation of the experimental solubility of the antimalarial artemisinin (Artemisia annua L.) in supercritical carbon dioxide is reported. Results were obtained using a static analytical method at 308.2, 318.2, and 328.2 K, and in a pressure range from 10.0 up to 25.0 MPa. Solubility experimental data were correlated with three density-based models (Chrastil, Bartle, and Méndez-Santiago−Teja models) and with two cubic equation of state (EOS) models, namely, the Peng−Robinson EOS and the Soave−Redlich−Kwong EOS, together with the conventional van der Waals mixing and combining rules. Good correlation results were obtained between the calculated and the experimental solubility to all fitted models. Results clearly show the feasibility of processing this antimalarial drug using supercritical fluid technologies and processes.

CIBA photoinitiator Irgacure® 2959 is a highly efficient radical photoinitiator for UV curing systems. Furthermore, and due to its proven low cellular toxicity, this photoinitiator can also be employed in the photopolymerization of polymers and copolymers intended for biomedical and tissue engineering applications, not only in conventional pharmaceutically accepted liquid solvents, but also in supercritical CO2 (scCO2). In this work we report the experimental measurement and correlation of the solubility of Irgacure® 2959 in scCO2. Results were obtained using a static analytical method, at 308.2, 318.2 and 328.2 K, and in a pressure range from 10.0 up to 26.0 MPa. Experimental data were correlated with three density-based models (Chrastil, Bartle and Méndez-Santiago-Teja models) and with an equation-of-state (EOS) model: the Peng-Robinson cubic equation of state (PR-EOS) together with the conventional van der Waals mixing and combining rules. Several different sets of solid properties, estimated by different methods available in literature, were used in EOS correlations. The importance of the estimation methods used for the determination of solid properties (namely sublimation pressure) was discussed in terms of correlation results quality.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microspheres containing flurbiprofen were prepared by an oil-in-water emulsion solvent evaporation method, in order to develop a particulate drug delivery system for localized administration. A response surface method (RSM) using a central composite design was employed to evaluate the effect of the poly(vinyl alcohol) (PVA) (%, w/v) concentration in the aqueous phase and the PHBV concentration in the organic phase (%, w/v) on some of the resulting microspheres properties. The response variables were the encapsulation efficiency (EE), the mean particle size, the width of particle size distribution (expressed by the SPAN value) and the required time for the in vitrorelease of 50% of the encapsulated drug (t50). Second-order polynomial and linear equations were fitted to experimental data and were also used to interpret the results. Results indicated that the concentration of the stabilizer (PVA) showed a highly negative effect on the EE probably due to the increased drug solubility in the aqueous phase as a result of the higher PVA concentrations. Particle diameter mean size increased with the increased polymer concentration while the width of the particle size distribution was found to decrease with the increase of the stabilizer agent. Finally, results indicated that none of the investigated variables presented a significant effect on the t50% values.

O presente trabalho visa analisar do ponto de vista jurídico-legal a realização de eventos que promovem rodeios no Brasil. Para tanto, além de abordar questões históricas, dar-se- á destaque a legislação pátria, bem como o posicionamento jurisprudencial. De modo que, será visto que as provas que caracterizam o chamado rodeio completo foram regulamentas, em âmbito nacional, no ano de 2001, após intensas campanhas em favor da sua regulamentação e, também, constantes ações judiciais contra as provas. Nesse passo, será tratada a disposição constitucional acerca do direito animal, com base no artigo 225, § 1º, inciso VII. Assim, o trabalho tem por objetivo descrever e analisar o processo de regulamentação dos rodeios, passando por cada modalidade. Bem como, fazer considerações a respeito da importância das fiscalizações nos eventos, para averiguação do cumprimento das normas, a fim de que sejam garantidas condições dignas aos animais envolvidos.

The main purpose of this work is the preparation and development of several controlled drug delivery systems built with natural polymers and suitable for different applications, like for colon-specific drug delivery or for the localized and prolonged delivery of drugs. With this objective, three potential controlled drug delivery systems, based on natural polymers, were prepared and characterized. In the first investigated system, the natural occurring polyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV, was processed in microparticles loaded with the hydrophobic drug flurbiprofen, by means of an oil-in-water emulsion/extraction solvent evaporation method, using chloroform as the organic phase and polyvinyl alcohol (PVA) as the emulsion stabilizer. A central composite experimental design was employed to evaluate the effect of two process variables – the polymer concentration in the organic phase and the surfactant concentration in the aqueous phase - on some of the final microparticles properties, specifically the encapsulation efficiency of the drug, the mean particle size, the width of the particles size distribution, and the required time for the in vitro release of 50% of the encapsulated drug (t50%). The statistical analysis of the implemented experimental design revealed that the two investigated variables had a significant and opposite effect on the encapsulation efficiency of the drug. Also, it was found that the microparticles mean particle size increased with increasing concentrations of PHBV in organic phase and that the concentration of the surfactant in the aqueous phase played a critical role in the aggregation degree of the microparticles. It was concluded that a minimum PVA concentration was required to stabilize the oil-in-water emulsion and, in this way, obtain non-aggregated particles. The in vitro flurbiprofen release profiles from PHBV microparticles were very similar for all the prepared formulations, showing that more than 90% of the drug was released in the first eight hours of the essay. The time for the in vitro release of 50% of the encapsulated drug, t50%, was not significantly influenced by any of the two investigated variables. The comparison between the release profiles of flurbiprofen from the PHBV microparticles and the dissolution profile of the pure drug lead to the conclusion that the drug was essentially dispersed at the surface of the microparticles, rather than effectively entrapped in the polymeric matrix. Although the investigated formulations didn’t led to an effective immobilization of the flurbiprofen in the PHBV microparticles, this objective can be achieve with further investigation, namely by the manipulation of the drug/polymer mass ratio used in the microparticles preparation, among other variables. With the flurbiprofen effectively immobilized in the microparticles, it will be possible to then optimize the drug release profile in order to obtain a controlled and prolonged release of the immobilized flurbiprofen, suitable for the use of the microparticles as localized and prolonged drug delivery systems. In the second investigated system, the polysaccharide pectin was chemically modified by introducing, in its structure, vinylic or methacrylic terminal functional groups. The functionalized pectin derivatives, alone or together with the macromer poly(ethylene glycol) diacrylate (PEGDA), were transformed in chemical hydrogels by UV-induced free radical reticulation. In vitro drug release studies were used to evaluate the behavior of the produced hydrogels as controlled drug delivery systems. For this purpose, two low molecular weight hydrophilic drugs (gentamicin sulphate and sodium flurbiprofen), and two model proteins (bovine serum albumin (BSA) and lysosyme), were incorporate in the hydrogels during their formation and subsequently released in vitro. It was concluded that the extension of the chemical modification of pectin, which was carried out in a heterogeneous environment, was limited/controlled by the accessibility of the OH groups of the polysaccharide, which, in turn, was directly controlled by the swelling degree of the polysaccharide particles in the reaction solvent. The two low molecular weight hydrophilic drugs were rapidly liberated from the hydrogels. The release profiles revealed that, in approximately four hours, the entire incorporated drug was released. On the other hand, the in vitro release studies of the model proteins revealed an incomplete release of the incorporated proteins, probably because a fraction of protein was physical adsorbed in to polymeric matrix and/or covalently bounded to it. The presence of pectinolytic enzymes in the release medium result in a higher fraction of BSA released from the hydrogels, supposedly due to the enzymatic degradation of the tridimensional network structure of the polymer matrix. The results obtained with this work show that the produced hydrogels are suitable to be use as colon-specific drug delivery systems, especially of proteins. In the third and last investigated system, sponges of pectin and chitosan, prepared by the freeze-drying of the insoluble polyelectrolyte complexes (PECs) formed between the two polysaccharides, were produced and characterized. Three pectin/chitosan PECs sponges were prepared, using different initial proportions of the two polysaccharides. The three sponges, independently of the used proportions, had very similar compositions, being composed mainly from pectin (74 to 78%, mass percentage). The sponges were submersed in aqueous solutions, either at pH 2 or pH 7.4, and the weight loss was record during six weeks. The results revealed a continuous weight loss, attributed to the gradual liberation of polymers chains, as a consequence of the progressive loss of the ionic interactions established, during PECs formation, between the COO- groups of pectin and the NH3+ groups of chitosan. The composition analysis of the sponges during dissolution time, and their FTIR spectra, revealed that, at pH 2, the weight loss of the sponges was caused, equally, by the loss of pectin and chitosan. On the other hand, it was concluded that, at pH 7.4, the weight loss of the sponges was mainly due to the loss of pectin. A preliminary evaluation of the sponges as controlled drug delivery systems was made, by the incorporation of BSA in the sponges followed by the in vitro release, at pH 2 and pH 7.4. The in vitro release profiles obtained suggest that the released of the protein from the sponges is controlled by the strong interactions established between the protein molecules and the polymeric matrix. This preliminary study indicates that the produced PECs matrixes can be use to immobilized proteins and built colon-specific delivery systems of this type of biomacromolecules. In the three works presented in this Thesis it was possible to obtained significant conclusions that can be used in the future as basis for the continuation of the development of the different controlled drug delivery systems proposed in this work.