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 do papel da proteína multifuncional APE1/Ref-1 sobre a resposta inflamatória na meningite bacteriana

Despite advances in antibiotic therapy, bacterial meningitis (BM) remains with high mortality and morbidity rates in worldwide. One important mechanism associated to sequels during disease is the intense inflammatory response which promotes an oxidative burst and release of reactive oxygen species, consequently leading to cell death. Activation of DNA repair enzymes during oxidative stress has been demonstrated in several neurological disorders. APE1/Ref-1 is a multifunctional protein involved in DNA repair and plays a redox function on transcription factors such as NFkB and AP-1.The aim of this study was assess the role of APE1/Ref-1 on inflammatory response and the possibility of its modulation to reduce the sequels of the disease. Firstly it was performed an assay to measure cytokine in cerebrospinal fluid of patients with BM due to Streptococcus pneumoniae and Neisseriae meningitides. Further, a cellular model of inflammation was used to observe the effect of the inhibition of the endonuclease and redox activity of APE1/Ref-1 on cytokine levels. Additionally, APE1/Ref-1 expression in cortex and hippocampus of rat with MB after vitamin B6 treatment was evaluated. Altogether, results showed a similar profile of cytokines in the cerebrospinal fluid of patients from both pathogens, although IFNy showed higher expression in patients with BM caused by S. pneumoniae. On the other hand, inhibitors of APE1/Ref-1 reduced cytokine levels, mainly TNF-α. Reduction of oxidative stress markers was also observed after introduction of inhibitors in the LPS-stimulated cell. In the animal model, BM increased the expression of the protein APE1/Ref-1, while vitamin B6 promoted reduction. Thereby, this data rise important factors to be considered in pathogenesis of BM, e.g., IFNy can be used as prognostic factor during corticosteroid therapy, APE1/Ref-1 can be an important target to modulate the level of inflammation and VIII oxidative stress, and vitamin B6 seems modulates several proteins related to cell death. So, this study highlights a new understanding on the role of APE1/Ref-1 on the inflammation and the oxidative stress during inflammation condition

Aplicação de nanopartículas de quitosana com potencial de adjuvante na produção de soro contra o venneno do escorpião Tityus serrulatus

In Brazil, several species of scorpions are known to cause accidents which can lead to death, which are mainly belonging to the genus Tityus. The scorpion Tityus serrulatus is the main responsible for more severe cases. Anti-scorpion serums are routinely produced by various institutions, despite their effectiveness, quality and action depends on how quickly treatment is started. Studies have been developed in the search for appropriate technologies to encapsulate and release recombinant or natives proteins capable of inducing antibody production. In this context, chitosan copolymer which can be obtained from the partial deacetylation of chitin or in some microorganisms and it is biocompatible and biodegradable has been widely used for this purpose. This study aimed to search for a system release from chitosan nanoparticles for peptide / protein of the venom of the scorpion T. serrulatus, able to provide a new model of immunization in animals, in order to obtain a potential novel polyclonal serum, anti-venom T. serrulatus. The chitosan nanoparticles were prepared by ionic gelation with polyanion tripolyphosphate (TPP). After standardizing the concentrations of TPP and chitosan was evaluated the efficiency of incorporation of bovine serum albumin (BSA) and scorpion venom, showed particle size compatible with the intended purpose. The particles showed adequate size around 200nm. The crosslinking was confirmed by absorption spectroscopy in the infrared. After verified the high encapsulation efficiency (EE) for acid bicinconínico method (BCA) protein assay and the particle size distribution, the success of the technique was proven and the potential for in vivo application of nanoparticles. The experimental animals were vaccinated and the antibodies measured by ELISA

Desenvolvendo e gerenciando compostagem de resíduos sólidos urbanos: para geração de renda e repasse de tecnologia à acrevi

Nowadays, as well as in the past decades, the dumping of biodegradable organic waste in landfill is common practice in Brazil, as well as in most parts of the world. Nevertheless due to its rapid decomposition and release of odors, this practice hamper’s the operation and implementation of a recycling system. These facts encouraged our research to find an efficient system for the management of organic waste, not only for the use of official workers responsible for managing these wastes, but also for non-governmental institutions. The Recycling for Life Community Association – ACREVI (Associação Comunitária Reciclando para a Vida), together with the municipal authorities of Mossoró-RN, Brazil, have assumed the social role of collecting and recycling solid waste produced by most of the local population. However, it was observed that the organic waste it collected was not receiving any treatment. This present work aims to make compost with mixed waste (green waste and organic household), and then do chemical analysis of the material in view to use the waste as organic fertilizer. The objective being: to share the knowledge acquired by putting it into a very simple language accessible to people with little education. The experiment was conducted at ACREVI, Mossoró (RN), and the compost was obtained following the method "windrow", forming three cells (I, II, III) with conical shape, dimensions of 1.6 meters and 2.0 meters in diameter for cells I and II, and 1.0 meters high and 2.0 meters in diameter for cell III. The process was accompanied by analysis: CHN elemental, a variation of cell temperature, humidity, pH, TKN, bulk density, nutrients and heavy metals. Stabilized organic compounds reached the C/N ratio of 10.4/1 cell I and 10.4/1 in the cell II in the cell, showing how good soil conditions, with potential to improve the physical properties of any soil and pH acid soils, has presented the cell III at the end of the process the C/N 26/1, is a high ratio may be associated with the stack size III, thus changing the optimal conditions for the occurrence of the process. The levels of heavy metals in the analyzed compounds were lower than those established by the SDA normative instruction, Nº 27, of 5 June, 2006. The use of pruning trees and grass are used in small-scale composting, while generating a quality compost in the final process, it also created an important condition for a correct sizing of the composting piles. Under the studied conditions it is not advisable to use cells with a height of 1.00 m in height and 2.00 m in diameter, as these do not prevent the rapid dissipation of heat and thus can not be a good product at the end of composting. The composting process in the shed of the association and the preparation of the primer enabled the development of an alternative technology to generate income for members of ACREVI.