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

Bioactive ceramic-reinforced composites for bone augmentation

Biomaterials have been used to repair the human body for millennia, but it is only since the 1970s that man-made composites have been used. Hydroxyapatite (HA)-reinforced polyethylene (PE) is the first of the ‘second-generation’ biomaterials that have been developed to be bioactive rather than bioinert. The mechanical properties have been characterized using quasi-static, fatigue, creep and fracture toughness testing, and these studies have allowed optimization of the production method. The in vitro and in vivo biological properties have been investigated with a range of filler content and have shown that the presence of sufficient bioactive filler leads to a bioactive composite. Finally, the material has been applied clinically, initially in the orbital floor and later in the middle ear. From this initial combination of HA in PE other bioactive ceramic polymer composites have been developed

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

Investigation of relationships through which biodynamic growing practices affect plant growth and nutrient composition : a thesis presented in partial fulfilment of the requirements of the degree of Master of Science in Soil Science at Massey University

Author also known as Gillian Leslie ColeMore research attention has been paid to development of indicators of soil quality in relation to environmental sustainability than to food quality. Challenges in measuring and showing relationships between soil quality, food quality and human health are discussed. Comparative and long-term studies have shown that organic and biodynamic farming methods and use of composts and manures favourably affect soil quality, enhancing organic matter content and soil organism activity. However, measured effects on food quality have been lacking or inconsistent. Antioxidants, nitrates, trace elements, protein quality and ratios between element concentrations can be measured in assessing food quality. Many of these factors vary considerably with growing conditions and soil management techniques. Effects of factors such as water, light, soil type, variety and nutrient supply on lettuce growth, lettuce nutrient requirements, and recent research into effects of light on plant signalling and nitrogen metabolism arc reviewed and discussed. Recent research into factors influencing food quality has focussed on integration of growth and differentiation forces into "Vital quality" food. The biodynamic field-spray preparations 500 and 501 are used to balance effects of growth or "shade" forces from humus and fertilisers with the differentiating or "light' forces on plants. Literature indicates that the preparation 501 (silica-spray) appears to increase plant nutrient assimilation and production of more complex organic acids. Similar effects have been found for silica compounds applied to soil or nutrient solution. The main objective of the experimental work conducted for this thesis was to investigate whether relationships exist between soil management techniques and application of biodynamic sprays and plant product quality. Transplanted lettuces (cv. Canasta) were grown in a factorial designed field trial on Te Puke Series sandy loam with six treatments: control, soluble fertilisers (DAPCAN) and compost, each with, or without, biodynamic field-sprays 500 (twice) and 501 (3 times). High variability between plants within treatments and small differences between treatment means for most parameters measured prevented many statistically significant differences or relationships being found. Compost amendments appeared to enhance water and nutrient uptake during a dry season. However compost application at a rate to provide equivalent nitrogen to the soluble fertilisers resulted in high leaf concentrations of nitrates and potassium and low DM% and concentrations of sugars, antioxidants, calcium and magnesium. Plants in treatments given compost had highest yields; highest N, P and K concentrations at 28 days from transplanting (DAT); and highest K at 48 DAT. Plants in treatments given soluble fertilisers had highest Ca, Mg, Fe, Zn. and Cu concentrations and greater Ca: P and K: Ca + Mg ratios at 48 DAT. Application of biodynamic field-sprays appeared to have different effects on the plants in plots, depending upon whether they received compost or not. Plants in treatments given field-sprays but no compost had generally small head weight, greater dry matter % and root: shoot ratios at 28 DAT, and highest crude protein and Ferric reducing ability of plasma (FRAP) antioxidant concentration at 48 DAT. Plants in the biodynamic treatment, given compost and field-sprays, had highest P uptake between 28 and 48 DAT and highest fresh-weight at 48 DAT. Measurements of nitrate and sugar contents of leaf cell sap and amino acid concentrations in leaves yielded few, or no, significant differences between treatment means. Microbial activity measured by soil respiration ex situ at 28 DAT was highest in composted plots and lowest in sprayed plots. Measurement of AM fungi colonisation of roots gave inconclusive results. In a sensory evaluation, no significant differences in taste, bitterness, sweetness and preference ranking were found between lettuces from the different treatments. A greenhouse pot trial was undertaken to study the effects of the biodynamic silica spray in more detail. Lettuce transplants (cv. Cos Little Gem) were grown in the same soil and biodynamic compost as were used in the first trial and preparation 500 applied. Half the plants were sprayed 3 times with preparation 501. Measurements before and after the last spray time yielded insignificant differences in light absorption at most wavelengths, net photosynthesis and nitrate, sugar and amino acid concentration in leaves. Silica sprayed plants had higher rates of transpiration and stomatal conductance and higher estimated light absorption of blue and near infrared wavelengths 21/2 hours after spraying. Mainly inconclusive effects of treatments were due partly to the large natural plant to plant (within replication) variation. It was concluded that organic and biodynamic management of lettuces may result in some favourable quality attributes compared to soluble fertilisers but not necessarily all. Results are likely to be specific to particular climatic and soil conditions. It is recommended that further trials be carried out to evaluate influences of biodynamic practices on vegetable food quality in controlled, well-replicated conditions, to improve likelihood of showing statistical differences between treatments. Such trials are needed in a variety of soil, climatic and management conditions, to better understand how different conditions and their interactions affect food quality parameters. Relationships between biodynamic preparation application, soil biota populations and activity, plant metabolism and food product quality, particularly nitrogen assimilation into complex molecules such as essential amino acids, should be explored

Spray drying as a reliable route to produce metastable carbamazepine form IV

Carbamazepine is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least five polymorphic forms. Metastable form IV was originally discovered from crystallisation with polymer additives however has not been observed from subsequent solvent only crystallisation efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic carbamazepine solution. Characterisation of the material was carried out using diffraction, SEM and DSC. In situ Raman spectroscopy was used to monitor the spray dried product during the spray drying process. This work demonstrates spray drying provides a robust method for the production of form IV carbamazepine and the combination of high supersaturation and rapid solid isolation from solution overcomes the apparent limitation of more traditional solution crystallisation approaches to produce metastable crystalline forms

Hydroxyapatite coating on titanium by a low energy plasma spraying mini-gun

Plasma-sprayed hydroxyapatite (HA) coatings are used on metallic implants to improve osseointegration and bone growth. The purpose of this work was to determine the microstructure and composition of HA coatings obtained with a newly developed low energy plasma spray mini-gun employing an HA feedstock powder with smaller granulometry than that commonly used. The microstructure and the phase composition of the coatings obtained by varying the number of mini-gun runs were examined using scanning electron microscopy, X-ray diffraction and Fourier transform infrared and micro-Raman spectroscopy. In all cases, the results indicate the presence of an amorphous phase and oxyapatite in the coatings due to hydroxyl group removal. No other foreign crystalline phases were detected. The absence of foreign phases was attributed to the fast cooling rate of the small particles used in the experiments and the low amount of energy employed with the mini-gun. Decomposition in the υ1PO4 region of the Raman spectra allowed a semi-quantitative evaluation of the phase contents as a function of the number of runs. Micro-Raman spectroscopy appears to be a powerful technique providing comprehensive and localised information concerning calcium phosphate phases in coatings

Safer selection and use of pesticides: Integrating risk assessment, monitoring and management of pesticides

Crop Production/Industries,

Drop-charge correlations for polydisperse electrostatically atomized liquid sprays

In many applications liquid sprays are atomized using electrostatic methods, and typically these spray plumes containing drops that have a range of diameters. To understand and predict the dynamics of polydisperse electrically charged spray plumes, knowledge of how the electrical charge is distributed amongst the drops is required. This has been achieved by post-processing phase Doppler anemometry data for two electrostatically atomized liquid sprays and fitting the drop diameter-charge correlation to an assumed relationship of form q=ADn, Here q and D are drop charge and diameter and n and A are empirical constants that describe the correlation. Values of n and A were calculated to be 2.1 to 2.9 and 5.8 ×10-5 for a spray of specific charge 1.8 C/m3 and 2.1 to 3.2 and its value of A is 2.5×10-4 for a spray of specific charge 1.2 C/m3. It was found that the mean drop charge, for all drop diameters, for both data-sets, was almost always less than the drop Rayleigh limit. This latter fact gives confidence in the procedure used since no restriction was placed on this parameter during the processing. We also estimate the distribution of drop charge about the mean value and as a function of diameter and suggest that small drops possess higher rms charge levels