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

Emulsões de óleo de copaíba: determinação do equilíbrio hidrófilo-lipófilo crítico (EHLC), propriedades e estabilidade físico-químicas

Durante as últimas décadas, as indústrias farmacêuticas têm despertado grande interesse em óleos vegetais e vários extratos de planta por causa da sua baixa toxicidade e alta biodegrabilidade. O óleo de copaíba (Cop) é usado in natura na medicina popular como anti-inflamatório e antimicrobiano para tratar várias doenças, tais como inflamação da garganta, úlceras e infecções urinárias e pulmonares. Emulsões são sistemas dispersos termodinamicamente instáveis que consistem em dispersões de gotículas microscópicas em outro líquido imiscível. O objetivo deste trabalho foi preparar diferentes emulsões de Cop, determinar o EHL crítico deste óleo e avaliar a sua estabilidade, além de realizar estudos comparativos entre diferentes métodos de construção de diagramas de fases. As emulsões foram preparadas pelo método de inversão de fases variando as proporções de EHL de 4,7 a 16,7. A estabilidade foi determinada por vários métodos e os diagramas de fases foram produzidos pelo método de titulação usando diferentes procedimentos de agitação. As emulsões a base de Cop com EHL entre 12,7 e 15,7 foram as mais estáveis. As emulsões apresentaram boa estabilidade em curto e longo prazo, aspecto leitoso e baixos valores de índice de cremagem. Diferentes sistemas coloidais foram produzidos a partir dos diagramas de fases dependendo do processo de agitação. Baseado nesses métodos, o valor determinado de EHL do Cop foi 14,8, as emulsões permaneceram estáveis por mais de um ano e estes resultados indicam que o estudo das emulsões de Cop pode ser um promissor veículo de liberação tópica de fármacos e ativos cosméticos

Análise in vitro da atividade antifúngica e de toxicidade da anfotericina B pré-aquecida

The aim of this work was to evaluate how an aqueous micellar system containing Amphotericin B (AmB) and sodium deoxycholate (DOC) can be rebuilt after heating treatment. Also a review of the literature about the new physicochemical and biological properties of this new system was carried out. Afterwards, heated (AmB-DOC-H) and unheated (AmB-DOC) micelles were subsequently diluted at four different concentrations (50mg.L-1, 5mg.L-1, 0.5mg.L-1 and 0.05mg.L-1) to perform the physicochemical study and, then, the pharmacotoxicity assay, in which two cell models were used for the in vitro experiments, Red Blood Cells (RBC) from human donors and Candida parapisilosis (Cp). While potassium (K+) and hemoglobin leakage from RBC were the used parameters to evaluate the acute and chronic toxicity, respectively, the efficacy of AmB-DOC and AmB-DOC-H were assessed by K+ leakage and cell survival rate from Cp. The spectral study revealed a slight change on the aggregate peak from 327nm to 323nm for AmB-DOC-H compared to AmB-DOC. Concerning the toxicity, although AmB-DOC and AmB-DOC-H presented different behavior for hemoglobin leakage, AmB-DOC produced higher leakage than AmB-DOC-H at high concentrations (from 5mg.L-1) with values tending to zero. However, concerning K+ leakage, both AmB-DOC and AmB-DOC-H, showed similar profile for both cell models, RBC and Cp (p<0,05). AmB-DOC-H and AmB-DOC also revealed similar profile of activity against Cp with equivalent survival rate. In short, the AmB-DOC-H showed much less toxicity than AmB-DOC, but remained as active as the late one against fungal cell. Therefore, the results highlight the importance of this new procedure as a simple, inexpensive and safe alternative to produce a new kind of micelle system for treatment of systemic fungal infections

Anfotericina b pré-aquecida: um novo sistema terapêutico para infecções fúngicas

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Influência de fármacos lipofílicos na estabilidade de emulsões de uso terapêutico

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Qualidade de frutos de cajá-manga armazenados sob diferentes temperaturas

O presente trabalho teve como objetivo determinar o efeito de diferentes temperaturas de armazenamento na qualidade de frutos de cajá-manga. Os frutos de cajá-manga foram obtidos junto ao CEAGESP - Companhia de Entrepostos e Armazéns Gerais de São Paulo, e transportados em caixas isotérmicas para o Laboratório onde foram selecionados quanto à aparência, estádio de maturação, ausência de danos físicos, depois sanitizados em solução de 50 ppm de cloro livre e acondicionados em bandejas de poliestireno expandido, envolto por filme de policloreto de vinila (PVC). O delineamento experimental utilizado foi o inteiramente casualizado, com três tratamentos (4ºC, 8ºC e 25ºC) e 5 épocas de avaliação (0; 3; 6; 9 e 12 dias após a instalação do experimento). em cada coleta, foram avaliadas a firmeza, a acidez titulável, os sólidos solúveis, o teor de ácido ascórbico, a cor da casca e, também, a liberação de CO2 pelos frutos ao longo do tempo. Foi observado que baixas temperaturas prolongam a vida útil dos frutos e que a temperatura de armazenamento influencia nas características avaliadas, sendo a temperatura de 8ºC a mais adequada para o armazenamento dos frutos de cajá-manga.

Determinação de parâmetros de qualidade para formas farmacêuticas homeopáticas

All medicine, whether allopathic or homeopathic, must go through strict quality control, which must ratify their characteristics throughout the period of validity. During the time of preparation and storage, solutions of the drugs are in permanent contact with packaging materials that can release undesirable substances to the solution. Several factors may influence the release of packing materials, and factorial design (FD) is a useful tool for analyzing the phenomenon. The aim of this study was the determination of quality parameters for Homeopathic solid (globules) and liquid (drops) dosage forms. It was carried out analysis in homeopathic globules for weight variation, mechanical strength, and moisture content uniformity. For liquid preparations, standard solutions were prepared from natural rubber bulbs, which were subjected to exhaustive extraction with two ethanol solutions (30 and 70%) in the ultrasonic bath for 20 minutes at 25°C and 50°C in three successive cycles. Studies of transfer have been made within five days, by spectrophotometric analysis in the UV region at 312 nm with λmáx and 323 nm for samples in 70% ethanol and 30% respectively. PH values were analyzed. We also conducted two FD studies, where the first, the three-level variables were solvent (chloroform, ethanol and nhexane), sample mass (30, 60 and 90mg), particle size (large disk, small disk and powder sample). In the second study, the solvent level variables were different ethanolic degrees (EtOH 30%, 70% and pure). The percentage of lending in the solutions was 5.5%, 12.4%, 24.2% and 41% of the total estimated in the reference solution. The values of rate constants of transfer were determined in the order of 0.0134 days-1 and 0.0232 days-1 in absorbance values, the solutions in ethanol at 30% and 70% respectively. These results suggest that the speed of transfer of materials from rubber is affected both by the nature of the vehicle as by the temperature

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

Preparação e caracterização de sistemas emulsionados contendo benznidazol

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Prostitutas entendidas: o que entender?

In this research, we propose a discussion from that observed in our field of work that women are prostitutes and who self-define understood. We check these women have sex with men by means of work and with women from the relationship of affection. We analyzed the practice of sexual activity as another possible expression of sexuality. There are many studies that deal with issues around the theme of prostitution and homosexuality in regard to various aspects and disciplines. Our proposal for study with these women is a topic that is on the agenda, as today, the theme of prostitution and homosexuality is well discussed within the Humanities in general. These new studies indicate about sexuality in a privileged place discussing values associated with the intimacy of the modern person, but also suggest that permeate discussions elements underlying the identity of women who have sex with women and men, the latter being, sexual activity mediated through the employment relationship by the financial interest, because according to our informants, prostitution is a job. From the reports of our participants / informants your answers fit the various brands that define the social field of possibilities of the sexual practices of individuals, raising questions about the origin and social class, family history, stage of life they are set of gender relations in the universe in which they live. All these elements provide the beacons to the process of shaping of subjectivity, understood as the social and biographical circumstances that define the direction I face this new constitution of the subject, it is defined by many theorists of the humanities, such as post-modern or modernity, and the insurgency that we have with the liberation movements that gays and lesbians were in question and make the politicization of sexuality

Limites e possibilidades do programa nacional de alimentação escolar enquanto estratégia de promoção da segurança alimentar e nutricional no municipio de Macaíba/RN

This dissertation aims to understand the importance of the National School Feeding as a strategy for ensuring the promotion of food and nutrition security in the municipality of Macaíba / RN, taking into account the implementation of the Law School Feeding, 11,947, 2009. The program was extended to all public basic education, youth and adults, in addition to ensuring that 30% of transfers from FNDE, were intended for the purchase of products from family farms. The survey was conducted with 160 students from public schools and farmers nesting Quilombo dos Palmares II, who produce on their land vegetables, fruits and cereals for their own consumption, for sale in local markets, in addition to providing for PNAE. The reciprocity between neighbors, such as mutual aid and sharing of common goods was noticeable in this group of farmers, since it was necessary to meet weekly deliveries of products to schools. As students, we applied a test of acceptability in two schools located in rural and in urban areas, to learn the opinion of ourselves in relation to school food consumed. It was concluded that to be most effective program in the region, there must be a better match in school menus, so that it can be attractive to students and to ensure greater use of fresh food, the main ingredient of same, practice of nutrition education in schools, to teach students the importance of food to health. In relation to local management, noted the need for adjustments bureaucratic as hiring staff for the departments, in order to be more agile in releasing payments to farmers, in addition to hiring assistants general services for schools, one Since the cooks exert dual role, the cooking while being responsible for cleaning the entire school environment. Government investments in the rural sector would be extremely valuable for farmers, since they need financial resources to purchase inputs, irrigation projects for gardens, availability of land for planting, transportation to facilitate the delivery of its products to schools and technical assistance more frequently

1930, a Paraíba e o inconsciente político da revolução: a narrativa como ato socialmente simbólico

This work is an attempt to show that the ideological conflict that has been developed by the hegemony of the 1930 Revolution historical events in Paraíba, conceptually turned into an insoluble social contradiction. It ocurred due to imaginary or formal resolutions of the literature that ended up by altering the epistemological rules of the relation between fiction and reality. The present work is based on The unconscious politics: a narrative as a socially symbolic act , book in which all the literary or cultural texts can and should be read as symbolic resolutions to insoluble social contradictions. From string to contemporary literature this phenomenon has been registered by the several ways of textual production turning the 1930 Revolution into one of the main elements which guides the political scene of Paraíba. The ideological groups still centered on the political resentment and committed to a political conflict forged the existence of two historical truths: one which suits the liberais , the winners, and another is of the 1930 conflict. This work argues in favour of the unconscious politics of the 1930 Revolution. This thesis considers necessarily the relation that the Paraibana society maintains with its past and how this past reaches in the present the liberation of a hidden and repressed truth through its narrativization. Beyond that, how the ideological partiality generated the political resentment through the way of thinking of the rivals under the perspective of the good and evil reveals its insoluble social contradiction. Process which comprehends varied narrative forms of the mass culture products and literary production, as in the methodological perspective pointed by Fredric Jameson that all literary or cultural texts can and shall be read as symbolic resolutions of true political and social contradictions. In the case of Paraiba we will have resolutions that search for the reasons which caused the death of João Pessoa: forgery and publicity of love letters, dispute over the official version of suicide commited by João Dantas, the man who assassinated João Pessoa

High-resolution electrocardiography in dogs under doxorubicin-induced cardiomyopathy

Determinaram-se a ocorrência de potencial tardio em cães com cardiomiopatia induzida pela doxorrubicina e sua relação com o desenvolvimento de arritmias ventriculares ou morte súbita. Sete cães adultos, sem raça definida, de ambos os sexos foram utilizados. A cardiomiopatia foi induzida por infusão venosa lenta de doxorrubicina (30mg/m²) em intervalos de 21 dias, até uma dose total cumulativa de 240mg/m². Os animais foram monitorados ecocardiograficamente. Após a confirmação da cardiomiopatia, foi feito o registro da eletrocardiografia de alta resolução. Potenciais tardios foram observados em dois animais que morreram subitamente poucos dias após.

Utilização intracoágulo de espuma fibrinolítica - preparação, caracterização e atividade in vitro de uma espuma de estreptoquinase e proposta de uma nova abordagem terapêutica

Foam was developed as a novel vehicle for streptokinase with the purpose of increasing the contact time and area between the fibrinolytic and the target thrombus, which would lead to a greater therapeutic efficacy at lower doses, decreasing the drug s potential to cause bleeding. Fibrinolytic foams were prepared using CO2 and human albumin (at different v:v ratios), as the gas and liquid phases, respectively, and streptokinase at a low total dose (100,000 IU) was used as fibrinolytic agent conveyed in 1 mL of foam and in isotonic saline solution. The foams were characterized as foam stability and apparent viscosity. The thrombolytic effect of the streptokinase foam was determined in vitro as thrombus lysis and the results were compared to those of a fibrinolytic solution (prepared using the same dose of streptokinase) and foam without the fibrinolytic. In vitro tests were conducted using fresh clots were weighed and placed in test tubes kept at 37 ° C. All the samples were injected intrathrombus using a multiperforated catheter. The results showed that both foam stability and apparent viscosity increased with the increase in the CO2:albumin solution ratio and therefore, the ratio of 3:1 was used for the incorporation of streptokinase. The results of thrombus lysis showed that the streptokinase foam presented the highest thrombolytic activity (44.78 ± 9.97%) when compared to those of the streptokinase solution (32.07 ± 3.41%) and the foam without the drug (19.2 ± 7.19%). We conclude that fibrinolytic foam showed statistically significant results regarding the enhancement of the lytic activity of streptokinase compared to the effect of the prepared saline solution, thus it can be a promising alternative in the treatment of thrombosis. However, in vivo studies are needed in order to corroborate the results obtained in vitro

Ceratomicose em equinos

O cavalo, dado o seu meio ambiente, está sujeito a afecções frequentes da córnea e da conjuntiva, tecidos oculares bastante expostos a bactérias e fungos, principalmente Aspergillus spp. e Fusarium spp. As ceratites ulcerativas bacterianas e fúngicas, bem como as ceratites fúngicas não ulcerativas, caracterizadas principalmente pelo abscesso estromal, são frequentes nessa espécie. Ocorrida a lesão inicial, perpetua-se um ciclo vicioso, com liberação de citocinas inflamatórias, que desencadeiam uma rápida e severa infiltração corneal por células polimorfonucleares. A córnea torna-se sujeita à destruição por enzimas proteolíticas liberadas pelos micro-organismos e por células inflamatórias, capazes de desencadear a dissolução estromal e a perfuração do bulbo ocular. O tratamento clínico para a resolução da doença corneal e o controle da uveíte reflexa deve ser agressivo e associado, muitas das vezes, à terapia cirúrgica. Este artigo discorre sobre a fisiopatologia e o tratamento da ceratomicose em equinos.