Didanosine-load chitosan microspheres and their formulation in mucoadhesive granules

Orientadores: Maria Helena Andrade Santana, Fernanda MartinsTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia QuimicaResumo: Neste trabalho foi desenvolvido um processo escalonável de produção de grânulos gastrorresistentes compostos de microesferas de quitosana contendo didanosina (ddI) incorporada. O processo global foi composto de três etapas, cujas condições operacionais foram otimizadas buscando-se preservar a forma ativa do fármaco, sensível ao pH ácido, e obter um produto de liberação modificada, mucoadesivo e gastrorresistente. A primeira etapa foi a incorporação da ddI, feita através da técnica da gelificação ionotrópica, utilizando tripolifosfato de sódio (TPP) como agente de reticulação e hidróxido de magnésio (Mg(OH)2) para assegurar a estabilidade do fármaco. As condições operacionais foram otimizadas pelo método do planejamento estatístico e análise de superfícies de resposta para as variáveis estatisticamente importantes: concentrações iniciais de quitosana, TPP e ddI. O máximo carregamento de ddI nas microesferas, 1433 mg de ddI/g de quitosana, foi obtido com 2,00 % de quitosana e 10,00 % de TPP. As microesferas obtidas apresentaram diâmetro médio de 11,42 µm, e a ddI incorporada foi liberada gradualmente em 2 h em suco entérico simulado. Na segunda etapa foram produzidos os grânulos contendo as microesferas, para os quais foram testados como excipientes: a própria quitosana, amido pré-gelificado e carboximetilcelulose. Os grânulos foram preparados por extrusão seguida de esferonização, e os mais promissores foram caracterizados quanto à mucoadesividade in vitro através da isoterma de adsorção da mucina e quanto à permeação ex vivo através do modelo de permeação pelo segmento intestinal invertido. Os resultados mostraram que os grânulos contendo 4,8 % de quitosana apresentaram maior afinidade pela mucina além de promover o aumento de 18 % na permeação da ddI pelo segmento duodenal comparado ao fármaco livre comercial. Os grânulos contendo as microesferas liberaram a ddI em 2 h, mais lentamente que os grânulos compostos pela mistura física de ddI e excipientes (10 min). Finalmente foi feito o revestimento entérico dos grânulos pela técnica da película, utilizando Eudragit® L30-D55 como polímero gastrorresistente. Por limitações de processo, o revestimento não produziu retenção total da ddI no meio ácido (77 %), porém em meio básico, os grânulos contendo as microesferas apresentaram liberação da ddI mais lenta que o medicamento gastrorresistente comercial. Esses resultados mostram a factibilidade da produção de grânulos de quitosana contendo microesferas incorporando fármaco sensível ao pH, em processo passível de escalonamento. Além disso, apresentam a ddI como um novo medicamento de liberação modificada para administração oral, com benefícios potenciais para a terapia da AIDS e conforto do pacienteAbstract: In this work a scalable process was developed for the production of gastroresistent granules containing chitosan microspheres, loaded with the drug didanosine (ddl). The global process included three stages, and the operational conditions were optimized in order to maintain the active form of the drug didanosine, which is sensitive to acidic pH conditions, and to obtain a final product with modified release, mucoadhesive and gastroresistent properties. The first stage included the encapsulation of ddl with the use of the ionotropic gelation technique with sodium tripoliphosphate (TPP) as the crosslinking agent and magnesium hydroxide (Mg(OH)2) to ensure the stability of ddl. The optimization was performed using Response Surface Methodology (RSM) with the important statistical variables: chitosan, TPP and ddl concentrations. The maximum ddl loading in microspheres of 1433 mg of ddl/g of chitosan, was obtained with 2.00% (w/v) chitosan and 10.00% TPP. The microspheres where observed to have an average diameter of 11.42 µm, and ddl was gradually released during a 2 h period in a simulated enteric fluid. In the second stage, the granules with microspheres were produced with different excipients: chitosan, pre-gelified starch and carboximethylcelullose. The granules were prepared by extrusion-spheronization and the most promising ones were characterized according to the in vitro granule mucoadhesiveness, determined through the adsorption isotherm of mucin, and the ex vivo granule absorption, determined using the everted gut sac technique. The results showed that the granules with 4.8 % (w/w) chitosan presented greater affinity for the mucin as well as promoting an increase of 18 % in the ddI absorption through the duodenal segment compared with commercial free drug. The granules containing the chitosan microspheres released ddl in a 2 h period, a longer release period compared to the granules composed of the mixture of the drug and excipients, where the drug was released in approximately 10 minutes. Finally the granules were coated by the film technique, using Eudragit® L30-D55 as the gastroresistent polymer. Due to the process limitations, the polymer coating did not retain the total amount of the drug in the simulated gastric fluid (77 %). However, in the simulated enteric fluid, the granules containing chitosan microspheres showed a slower release of ddI compared to the commercial gastroresistent granules. These results demonstrate that it is possible to produce granules with microspheres that encapsulate a drug sensitive to acidic pH conditions, in a process that is easily scaled up. The process also shows a new formulation of the drug ddl, with modified release kinetics for oral administration, with potential benefits for AIDS therapy, as well as providing more comfort to the patientDoutoradoDesenvolvimento de Processos BiotecnologicosDoutor em Engenharia Químic

Efeito da temperatura e do tamanho de partículas na adsorção do corante Remazol Amarelo Ouro RNL em carvão ativado

Textile industries have environmental problems due to high levels of COD and color. Adsorption is one of the most important processes used to remove color from effluent. Adsorption isotherms of Remazol Gold Yellow Remazol RNL reactive dye in activated carbon were determined. Two parameters were studied: temperature (30 and 40 degrees C) and particle size (1.70 +/- 0.30 mm e 3.00 +/- 0.40 mm). Results show that an increase in temperature or a decrease in particle size promotes in increase in the adsorption. the Langmuir-Freundlich equation was the best-fitted model for the experimental data.Universidade Federal de São Paulo, BR-09972270 São Paulo, BrazilCtr Biotecnol Amazonia, Manaus, Amazonas, BrazilUniv Estadual Oeste Parana, Toledo, Parana, BrazilUniversidade Federal de São Paulo, BR-09972270 São Paulo, BrazilWeb of Scienc

Análise físico-química de salames coloniais comercializados no município de Toledo, Estado do Paraná

Physical-chemical analysis of colonial italian type salami commercialized in Toledo, Parana state. Italian immigration in the west of Parana State contributed for the development of small meat industries. the colonial Italian-type salami is one of the main commercialized meat products in this region, therefore making necessary its quality evaluation. the aim of this work is to verify whether the composition of the colonial salami is in accordance with Brazilian law, and the nutritional facts information on the labels of these products. Four different marks of colonial Italian-type salami produced in the region of Toledo, Parana State and one great trade mark of Italian-type salami were herein evaluated. Properties like moisture, percentages of proteins, ashes, lipids and cholesterol were evaluated. We recorded a great discrepancy between values presented in the nutritional facts information and determined values, except for the industrialized salami. the moisture content was higher than the maximum levels recommended by the legislation. On the other hand, protein contents were lower than the minimum values recommended, and only the fat content matched the values established by Brazilian law. the cholesterol contents were lower than described on the labels when they contain them. According to the composition of the product and the Brazilian legislation, such salami could not be classified as Italian-type salami.Universidade Federal de São Paulo, BR-09972270 São Paulo, BrazilUniv Estadual Oeste Parana, Toledo, Parana, BrazilUniversidade Federal de São Paulo, BR-09972270 São Paulo, BrazilWeb of Scienc

Chitosan as flocculant agent for clarification of stevia extract

Stevia is used as a sweetener due to its low calorific value and its taste, which is very similar to that of sucrose. After extraction from dried leaves, stevia extract is dark in colour, and therefore needs to be whitened to increase acceptance by consumers. In this study we tested chitosan, a cationic polyelectrolyte, as flocculant agent for the whitening of the Stevia extract. Positive charges of chitosan can interact electrostatically with a counter-ion, sodium tripolyphosphate (TPP), and then chitosan precipitates. A factorial design was used to study the whitening process, in which Glycosides Removal, Colour Removal, Turbidity Removal and Soluble Solids Removal were evaluated. The studied factors were Chitosan Mass and pH of the TPP solution. The results showed that chitosan is a good flocculant agent, being able to flocculate both the glycosides and the pigments that make the extract coloured.UNIOESTE Centro de Engenharias e Ciências ExatasUNIFESP Centro de Ciências Exatas e da TerraUNIFESP, Centro de Ciências Exatas e da TerraSciEL

The effect of andiroba oil and chitosan concentration on the physical properties of chitosan emulsion film

Chitosan film is used as a dressing to heal burns. The physical and biological properties of the film can be modified by the addition of phytotherapic compounds. This work used the casting -solvent evaporation technique to prepare chitosan film containing andiroba oil (Carapa guianensis) which has anti-inflammatory, antibiotic, and healing properties. The objective of this study was to determine the effect of the concentrations of chitosan and andiroba oil on the physical properties of chitosan films. The emulsion films were evaluated concerning the mechanical properties and fluid handling capacity. Additionally, scanning electron microscopy and thermal analysis were performed. The results showed that the barrier and mechanical properties were affected by the addition of andiroba oil, and these may be modulated as a function of the concentration of oil added to the film. The thermal analysis showed no evidence of chemical interactions between the oil and chitosan.Sao Paulo Research Foundation (FAPESP)Univ Fed Sao Paulo UNIFESP, Inst Ciencias Quim Ambientais & Farmaceut, Lab Biotecnol & Prod Nat BION, Diadema, SP, BrazilUniv Fed Sao Paulo UNIFESP, Inst Ciencias Quim Ambientais & Farmaceut, Lab Biotecnol & Prod Nat BION, Diadema, SP, BrazilFAPESP: 2010/17.721-4Web of Scienc

Silver nanoparticles-composing alginate/gelatine hydrogel improves wound healing in vivo

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430450 nm in the ultraviolet-visible (UVVis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FTIR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.This research received funding from the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #443238/2014-6, #470388/2014-5), and from the Portuguese Science and Technology Foundation (FCT) projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Correction: Diniz et al. Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo. Nanomaterials 2020, 10, 390

In the original publication, there was a mistake in Figure 6 as published [...]info:eu-repo/semantics/publishedVersio

Efeitos da troca ionica em zeolitas na absorção de frutose

Orientadores: Francisco Maugeri Filho, Nadia Regina Camargo Fernandes MachadoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia de AlimentosResumo: A dextrana é um grupo de polissacarídeos de origem bacteriológica, consistituída por uma cadeia principal de moléculas de D-glucose unidas por ligações ?-1,6. O grau de ramificação, o peso molecular e outras propriedades da dextrana são muito específicas, variando conforme o microrganismo usado para a produção da dextrana-sacarase. Na produção da dextrana a partir da sacarose, também há a formação de frutose como produto secundário da reação. Diversos trabalhos e algumas patentes têm proposto a separação da mistura dextranafrutose utilizando resinas de troca iônica. Nenhum trabalho tem sido reportado utilizando zeólitas na separação desta mistura; porém, zeólitas Y na forma cálcica e bárica têm sido testadas na separação da mistura glicose-frutose. As zeólitas são aluminossilicatos cristalinos, com estrutura porosa, formada basicamente por tetraedros SiO4 e (AlO4)-. Cada tetraedro (AlO4)- induz uma carga negativa que é contrabalanceada por um cátion, chamado cátion de compensação, que confere à zeólita diferentes propriedades físico-químicas. Normalmente as zeólitas são sintetizadas com sódio como cátion de compensação e este pode ser trocado posteriormente. O objetivo deste trabalho é verificar o efeito da troca iônica em zeólitas na adsorção da frutose. As zeólitas sofreram trocas iônicas segundo um planejamento experimental tendo como parâmetros o cátion introduzido na troca (cálcio ou bário), o tempo de realização da troca (5 minutos ou 24 horas) e o tipo de zeólita (A e duas zeólitas Y com diferentes razões de silício/alumínio). As trocas iônicas foram realizadas em reator batelada sob agitação. Na primeira fase foram determinadas as isotermas de adsorção de frutose a 30°C para cada zeólita trocada variando a concentração de frutose de 5 a 150 g/L. Observou-se que as isotermas se comportaram como isotermas de Langmuir em concentrações menores que 150 g/L, sendo que as zeólitas Y de maior razão silício/alumínio apresentaram uma maior capacidade de adsorção, seguida pelas zeólita A e a zeólita Y de menor razão silício/alumínio. A capacidade de adsorção também foi maior para as zeólitas que apresentavam o cálcio como cátion trocado. Observou-se ainda que, quanto maior o tempo de troca iônica maior é a quantidade de cátions trocados pela zeólita e maior é a capacidade de adsorção da frutose. As zeólitas que não foram submetidas à troca iônica apresentaram capacidades de adsorção de frutose bem menores. Com base na análise das isotermas observou-se que a zeólita Y de maior razão silício/alumínio trocada com cálcio durante 24 horas apresentou melhor comportamento com relação à capacidade de adsorção. Com esta zeólita realizouse um teste de adsorÇão da frutose num meio contendo a dextrana, verificou-se que houve adsorção da frutose nestas condições, obtendo-se uma relação da ordem de 30 mg de frutose/g de zeólitaAbstract: Dextran is a polysaccharide group from bacteriological origin, composed by glucose units linked by ?-1,6 bonds. Branching, molecular weight and other properties are very specific and related to the micro-organism used to produce dextransucrase enzyme. Fructose is obtained as a secondary product by dextran synthesis from sucrose. Some reported works, many of them as patents, advise to separate fructose from dextran by ion-exchange resins. No article has been shown about fructose separation from dextran by zeolites, however zeolite type Y with Calcium and Barium has been tried in fructose separation from glucose. Zeolites are aluminium silicate with porous structure composed basically by Si04 and (Ab03f tetrahedrons. Each tetrahedron induces a negative charge in its structure that is balanced by a cation named compensation cation. It is usually synthesized with Sodium as compensation cation, which can be exchanged afterward. This cation gives zeolites differents phys.ical chemistry properties. This work verifies the effects of the ion-exchange in zeolites in the adsorption of fructose. Ion-exchange was carried out in a batch reactor according to experimentals designs with the following parameters: cation introduced (Calcium or Barium), exchanging time (5 minutes or 24 hours) and zeolite type (A and two zeolites type Y with different Silicon/Aluminium ratio). At first, were determined adsorption isotherm at 30°C for each ion-exchanged zeolite with concentration of fructose ranging from 5 to 150 g/L. The isotherm behaved like Langmuir Isotherm in concentration below 150 g/L, ,and the best capacity of adsorption were found in zeolite Y with the higl;1:est Silicon/Aluminium ratio, followed by zeolite A and the other zeolite Y with 10Vler ratio. The best capacity of adsorption was also obtained by zeolites exchanged with Calcium. The research showed that the longer the exchanging time were, the more cation were exchanged and the higher were the capacity of adsorption. Zeolites that were not ion-exchanged showed lower capacity of adsorption. The highest capacity of adsorption was found in zeolite type Y with highest Silicon/Aluminium ratio and exchanged with Calcium. This zeolite was tried in the adsorption of fructose from dextran procution medium. It was verified that this zeolite adsorbed fructose from dextran medium in the ratio of about 30 mg fructose/g zeoliteMestradoMestre em Engenharia de Alimento