Chitosan/carrageenan nanoparticles: effect of cross-linking with tripolyphosphate

Chitosan/carrageenan/tripolyphosphate nanoparticles were prepared by polyelectrolyte complexation/ionic gelation, the latter compound acting as cross-linker. The incorporation of the three components in the nanoparticle matrix was assessed by analytical techniques (FTIR, XPS and TOF-SIMS). Using chitosan/carrageenan nanoparticles as control, the effect of the cross-linker in the particles properties was studied. A decrease in size (from 450-500 nm to 150-300 nm) and in zeta potential (from +75 - +85 mV to +50 - +60 mV), and an increase in production yield (from 15-20% to 25-35%), and in stability (from one week to up to 9 months) were observed. Also, a correlation between positive to negative charge ratios in the formulations and the above characteristics was established. The small size and high positive surface charge make the developed chitosan/carrageenan/tripolyphosphate nanoparticles potential tools for an application in mucosal delivery of macromolecules

Inhalable fucoidan microparticles combining two antitubercular drugs with potential application in pulmonary tuberculosis therapy

The pulmonary delivery of antitubercular drugs is a promising approach to treat lung tuberculosis. This strategy not only allows targeting the infected organ instantly, it can also reduce the systemic adverse effects of the antibiotics. In light of that, this work aimed at producing fucoidan-based inhalable microparticles that are able to associate a combination of two first-line antitubercular drugs in a single formulation. Fucoidan is a polysaccharide composed of chemical units that have been reported to be specifically recognised by alveolar macrophages (the hosts of Mycobacterium). Inhalable fucoidan microparticles were successfully produced, effectively associating isoniazid (97%) and rifabutin (95%) simultaneously. Furthermore, the produced microparticles presented adequate aerodynamic properties for pulmonary delivery with potential to reach the respiratory zone, with a mass median aerodynamic diameter (MMAD) between 3.6-3.9 mu m. The formulation evidenced no cytotoxic effects on lung epithelial cells (A549), although mild toxicity was observed on macrophage-differentiated THP-1 cells at the highest tested concentration (1 mg/mL). Fucoidan microparticles also exhibited a propensity to be captured by macrophages in a dose-dependent manner, as well as an ability to activate the target cells. Furthermore, drug-loaded microparticles effectively inhibited mycobacterial growth in vitro. Thus, the produced fucoidan microparticles are considered to hold potential as pulmonary delivery systems for the treatment of tuberculosis.Portuguese Foundation for Science and Technology [PTDC/DTP-FTO/0094/2012, UID/Multi/04326/2013, UID/BIM/04773/2013]; CAPES-Brazil [BEX 1168/13-4

Dual antibiotherapy of tuberculosis mediated by inhalable locust bean gum microparticles

Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy. Microparticles were produced by spray-drying, at LBG/INH/RFB mass ratio of 10/1/0.5. The aerodynamic characterisation of microparticles revealed emitted doses of more than 90% and fine particle fraction of 38%, thus indicating the adequacy of the system to reach the respiratory lung area, thus partially the alveolar region. Cytotoxicity results indicate moderate toxicity (cell viability around 60%), with a concentration-dependent effect. Additionally, rat alveolar macrophages evidenced preferential capture of LBG microparticles, possibly due to chemical composition comprising mannose and galactose units that are specifically recognised by macrophage surface receptors. (C) 2017 Elsevier B.V. All rights reserved.National Portuguese funding through FCT - Fundacao para a Ciencia e a Tecnologia [PTDC/DTP-FTO/0094/2012, UID/BIM/04773/2013, UID/Multi/04326/2013, UID/QUI/00100/2013, PEst-OE/QUI/UI4023/2011

N,N '-dimethyl-N,N '-dicyclohexylsuccinamide: A novel molecule for the separation and recovery of Pd(II) by liquid-liquid extraction

N,N'-dimethyl-N,N'-dicyclohexylsuccinamide (DMDCHSA) is investigated as a potential molecule for the liquid-liquid extraction of Pd(II) from chloride solutions for the first time. The effect of several parameters on Pd(II) extraction, such as the contact period between both phases, hydrochloric acid, extractant and hydrogen ion concentrations, is evaluated. Pd(II) extraction equilibrium is very fast (30 s) and the extraction percentage (%E) increases with the HCI concentration in the aqueous phases, being higher than 60% for [HCl] > 5 M. The loading capacity of DMDCHSA for Pd(II) is reasonable (molar ratio extractant/metal higher than 16). Several stripping agents (e.g. distilled water, 1 M HCl, seawater and 20 g/L chloride solution as NaCl) were successfully used to transfer Pd(II) to a new aqueous phase, and data obtained from five successive extraction-stripping cycles suggest a good DMDCHSA stability pattern. Attempts to replace 1,2-dichloroethane (1,2-DCE) by commercial and more environmentally friendly diluents showed much worse %E for Pd(II). Selectivity tests with binary, ternary and more complex metal ion solutions were carried out to evaluate the performance of DMDCHSA towards Pd(II) recovery from 6 M HCl, when in presence of Pt(IV), Fe(III), Zn(II), Al(III) and Ce(III), metal ions usually present in solutions that may result from the hydrometallurgical treatment of spent automobile catalytic converters. It was generally observed that the additional metal ions do not affect the recovery of Pd(II) by DMDCHSA, although Fe(III) and Pt(IV) were co-extracted in a great extent. A solvent extraction (SX) scheme is proposed, based on a previous separation of Fe(III) with tributylphosphate (TBP) and on the selective and sequential stripping of Pt(IV) and Pd(II) from the loaded DMDCHSA with 0.01 M thiourea in 0.5 M HCI and seawater, respectively. The dependence of the Pd(II) distribution ratios on DMDCHSA and acidity, complemented with UV-Visible spectroscopy data, points out to DMDCHSA:Pd(II) extracted species with a 2:1 molar ratio and suggests the occurrence of an outer-sphere ion pair reaction, in which both [PdCl4](2-) and HCI are extracted

Inhalable spray-dried chondroitin sulphate microparticles: effect of different solvents on particle properties and drug activity

Spray-drying stands as one of the most used techniques to produce inhalable microparticles, but several parameters from both the process and the used materials affect the properties of the resulting microparticles. In this work, we describe the production of drug-loaded chondroitin sulphate microparticles by spray-drying, testing the effect of using different solvents during the process. Full characterisation of the polymer and of the aerodynamic properties of the obtained microparticles are provided envisaging an application in inhalable tuberculosis therapy. The spray-dried microparticles successfully associated two first-line antitubercular drugs (isoniazid and rifabutin) with satisfactory production yield (up to 85%) and drug association efficiency (60%-95%). Ethanol and HCl were tested as co-solvents to aid the solubilisation of rifabutin and microparticles produced with the former generally revealed the best features, presenting a better ability to sustainably release rifabutin. Moreover, these presented aerodynamic properties compatible with deep lung deposition, with an aerodynamic diameter around 4 μm and fine particle fraction of approximately 44%. Finally, it was further demonstrated that the antitubercular activity of the drugs remained unchanged after encapsulation independently of the used solvent.UID/Multi/04326/2019; SFRH/BD/52426/2013; ED481B 2018/071info:eu-repo/semantics/publishedVersio

Intravenous infusion of magnesium sulfate and its effect on horses with trigeminal-mediated headshaking.

BackgroundTrigeminal-mediated headshaking results from low-threshold firing of the trigeminal nerve resulting in apparent facial pain. Magnesium may have neuroprotective effects on nerve firing that potentially dampen signs of neuropathic pain. This hypothesis has not been investigated in horses with trigeminal-mediated headshaking.ObjectiveTo investigate head-shaking behavior in affected horses after IV magnesium sulfate infusion.AnimalsSix geldings with trigeminal-mediated headshaking.MethodsProspective randomized crossover study. Horses were controlled for diet and infused IV with 5% dextrose solution (DS; control solution at 2 mL/kg body weight [BW]) and MgSO4 50% solution (MSS at 40 mg/kg BW). Head-shaking behavior was recorded at times T0 (baseline, before infusion) and T15, T30, T60, and T120 minutes post-infusion. Venous blood variables such as pH, HCO3 - , standard base excess (SBE), Na+ , Cl- , K+ , Ca2+ , Mg2+ , total magnesium (tMg), glucose, and lactate were measured; strong ion difference (SID) and anion gap (AG) were calculated for each time point.ResultsBlood variables including pH, Na+ , Cl- , K+ , SID, AG, lactate, Ca2+ , tMg, and Mg2+ had significant changes with MSS as compared to DS treatment. Glucose, SBE, and HCO3 - did not have significant changes. A 29% reduction in head-shaking rate occurred after MSS treatment but no change occurred after DS treatment.Conclusions and clinical importanceAdministration of MSS IV increased plasma total and ionized magnesium concentrations and significantly decreased head-shaking behavior in horses with trigeminal-mediated headshaking

Les pratiques d’attention à santé dans les établissements psychosociaux: les effets du mode de production capitaliste

O modo de produção de bens materiais é correlato ao modo de produção de saúde e indica as formas de subjetivação possíveis em uma sociedade, portanto, está relacionado às maneiras como impasses sociais e psíquicos se materializam. Os conflitos da luta de classes produzem contradições, de maneira que é crucial observar que os sintomas desencadeadores das crises vêm enunciar objeção ao contexto social no qual emergiram. Partindo da análise organizacional, constatamos que os estabelecimentos institucionais de saúde mental no contexto do modo capitalista de produção têm servido para agenciar essas crises no sentido de dissuadi-las. Observa-se que, apesar dos avanços da reforma psiquiátrica brasileira, os estabelecimentos psicossociais ainda servem à adaptação social, produzindo subjetividades alienadas e reproduzindo formas históricas de dominação-subordinação, como a internação psiquiátrica e a medicalização da vida e do sofrimento.El modo de producción de bienes materiales se correlaciona con el modo de producción de salud e indica las posibles formas de subjetivación en la sociedad, por tanto, se refiere a la manera en que los puntos muertos sociales y psíquicos se materializan. Los conflictos de la lucha de clases producen contradicciones, por lo que es fundamental señalar que los síntomas desencadenantes de las crisis vienen a declarar una objeción al contexto en que surgieron. Con base en el análisis organizacional, constatamos que los establecimientos institucionales de salud mental han servido para administrar esas crisis en el sentido de disuadirlas. Se observa que, pese a los avances de la reforma psiquiátrica brasileña, los establecimientos psicosociales todavía sirven a la adaptación social, producen subjetividad alienada y reproducen formas históricas de dominación-subordinación, como la internación psiquiátrica y la medicalización de la vida y del sufrimiento.The mode of production of material goods is correlated to the mode of production of health and indicates the possible forms of subjectivation in a society, thus, the mode of production is related to the ways in which the social and psychic impasses materialize. Conflicts of the class struggle produce contradictions, so it is crucial to note that the symptoms that trigger the crises come to enounce an objection to the social context in which they emerged. Based on institutional analysis, we find that mental health institutions in the context of the capitalist mode of production have served to manage these crises in order to dissuade them. It is observed that despite the advances of Brazilian psychiatric reform, psychosocial establishments still serve social adaptation, producing alienated subjectivities and reproducing historical forms of domination-subordination, such as psychiatric hospitalization and medicalization of life and suffering.Le mode de production des biens matériels est corrélatif au mode de production de santé et indique les façons de subjectivation possibles dans une société, donc, soit lié à la manière comme les impasses sociales et psychique se matérialisent. Les conflits de lutte de classes produisent contradictions, de manière qu’est cruciale regarder que les symptômes que déclenchent des crises viennent à énoncer une objectivation au contexte socioculturel dans lequel ils ont émergé. À partir de l’analyse institutionnelle, on a constaté que les practices de santé mentale au sein du mode capitaliste de production ont servi pour traiter ces crises afin de les dissuader. On observe que, malgré les progrès de la réforme psychiatrique brésilienne, l‘établissement psychosocial sert encore à l’adaptation sociale, en créant des subjectivités aliénées et en reproduisant formes historiques de domination-subordination, comme l’hospitalisation psychiatrique et la médicalisation de la vie e de la souffrance

Otimização da operação de um reator de pirólise de resíduos sólidos industriais

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas. Programa de Pós-Graduação em Engenharia e Química.Neste trabalho é realizado o estudo do caso da reciclagem, por pirólise, de resíduos poliméricos provenientes de empresas da região nordeste do estado do Rio Grande do Sul, que são considerados críticos no que se refere ao volume gerado e ao grau de periculosidade. Os resíduos estudados foram: Polipropileno(PP), Acrilonitrila-Butadieno-Estireno(ABS) e resíduo de tinta de origem poliuretânica. Neste trabalho foi desenvolvida uma metodologia para otimizar a operação de um reator de pirólise multiprodutos, cujos maiores desafios são gerar produtos que sejam atóxicos e aproveitados no mercado a preços competitivos, remunerar o capital investido para desenvolver, montar e operar a planta de pirólise, e utilizar um método de otimização viável para um sistema de produção batelada multiprodutos. Para este propósito, o trabalho é composto por três partes principais: a) aquisição on line de dados, através de um sistema experimental montado em escala de bancada; b) levantamento de informações, em campo, sobre a região de inserção da planta de pirólise; e c) desenvolvimento de um código computacional para a otimização do reator pirolítico. A otimização da planta de pirólise multiprodutos consistiu na atualização do sequenciamento da produção e dos set points operacionais necessários para atingir os objetivos do planejamento de produção, dentro de um horizonte de tempo de um mês através da maximização de uma função lucro. Essa função envolveu dados técnicos e econômicos, como temperatura e tempo de batelada, preços e quantidades processadas e produzidas de resíduos e de óleos, respectivamente, quantidades consumidas e geradas de gases combustíveis e restrições de demanda de matérias-primas e produtos. Esse problema de otimização foi resolvido através de uma metodologia de solução utilizando Algoritmos Genéticos. O resultado é um código computacional flexível, que permite rescheduling para absorver as variações das necessidades de mercado, capacidade de produção e condições operacionais, dentro de um tempo computacional viável e que pode ser usado para vários resíduos, onde o rendimento de produtos e a energia envolvida no processo são determinados sem o conhecimento prévio da cinética e do calor das reações de pirólise

Inhalable antitubercular therapy mediated by locust bean gum microparticles

Tuberculosis remains a major global health problem and alternative therapeutic approaches are needed. Considering the high prevalence of lung tuberculosis (80% of cases), the pulmonary delivery of antitubercular drugs in a carrier system capable of reaching the alveoli, being recognised and phagocytosed by alveolar macrophages (mycobacterium hosts), would be a significant improvement to current oral drug regimens. Locust bean gum (LBG) is a polysaccharide composed of galactose and mannose residues, which may favour specific recognition by macrophages and potentiate phagocytosis. LBG microparticles produced by spray-drying are reported herein for the first time, incorporating either isoniazid or rifabutin, first-line antitubercular drugs (association efficiencies >82%). Microparticles have adequate theoretical properties for deep lung delivery (aerodynamic diameters between 1.15 and 1.67 μm). The cytotoxic evaluation in lung epithelial cells (A549 cells) and macrophages (THP-1 cells) revealed a toxic effect from rifabutin-loaded microparticles at the highest concentrations, but we may consider that these were very high comparing with in vivo conditions. LBG microparticles further evidenced strong ability to be captured by macrophages (percentage of phagocytosis >94%). Overall, the obtained data indicated the potential of the proposed system for tuberculosis therapy