Ana A. Matias

Effect of ionic liquids on human colon carcinoma HT-29 and CaCo-2 cell lines

The toxicity of ionic liquids, involving different classes of cations and different types of anions, was evaluated by a colorimetric assay with 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) in two colon carcinoma HT-29 and CaCo-2 cell lines. Confluent CaCo-2 cells can undergo spontaneously an enterocytic differentiation and represent a good in vitro model of normal human intestinal epithelium. Ionic liquids are highly promising due to their low vapour pressures, however, toxicity evaluation of these ionic liquids is of great importance to assess the risk of these ionic liquids to humans and the environment.

Evaluation of cardiovascular protective effect of different apple varieties - Correlation of response with composition

Epidemiological evidence supports the concept that diets rich in fruits and vegetables promote health and attenuate or delay the onset of cardiovascular disease (CVD). In particular, a reduced risk of CVD has been associated with apple consumption, probably due to the cholesterol-lowering effect of the main bioactive compounds, namely fibre and polyphenols. In this work, the effect of diet supplementation with 20% of three Portuguese apple cultivars (Bravo de Esmolfe, Malápio Serra and Golden), containing distinct phenolic and fibre concentrations, on serum lipid profile and oxLDL of male Wistar rats fed a cholesterol-enriched diet (2%) was evaluated. After 30 days, only Bravo de Esmolfe apple was able to decrease significantly serum levels of triglycerides, total and LDL cholesterol concentrations (reductions of 27.2%, 21.0% and 20.4%, respectively, in relation to the cholesterol-enriched diet group, P<0.05). The levels of oxLDL were also significantly improved with the consumption of this apple variety (reductions of 20.0% and 11.9%, in relation to the cholesterol-enriched diet group and control group, respectively, P>0.05) as well as with Malapio da Serra apple (reductions of 9.8% in relation to the cholesterol-enriched diet group, P<0.05). Correlation of the bioactive response with chemical composition showed that catechin, epicatechin, procyanidin B1 and β-carotene are the major phytocompounds responsible for the cholesterol lowering ability of apples. The antioxidant potential may have also contributed to this beneficial effect.

Phosphonium-based ionic liquids as modifiers for biomedical grade poly(vinyl chloride).

This work reports and discusses the influence of four phosphonium-based ionic liquids (PhILs), namely trihexyl(tetradecyl) phosphonium dicyanamide, [P(6,6,6,14)][dca]; trihexyl(tetradecyl) phosphonium bis(trifluoromethylsulfonyl)imide, [P(6,6,6,14)][Tf(2)N]; tetrabutyl phosphonium bromide, [P(4,4,4,4)][Br]; and tetrabutyl phosphonium chloride, [P(4,4,4,4)][Cl], on some of the chemical, physical and biological properties of a biomedical-grade suspension of poly(vinyl chloride) (PVC). The main goal of this work was to evaluate the capacity of these PhILs to modify some of the properties of neat PVC, in particular those that may allow their use as potential alternatives to traditional phthalate-based plasticizers in PVC biomedical applications. PVC films having different PhIL compositions (0, 5, 10 and 20 wt.%) were prepared (by solvent film casting) and characterised by Fourier transform infrared, thermogravimetric analysis, differential scanning calorimetry, dynamical mechanical thermal analysis, scanning electron microscopy/energy-dispersive X-ray/electron probe microanalysis, X-ray diffraction, transmittance, permeability towards oxygen and carbon dioxide, thermal degradation, contact angle measurement, water and vapour uptake, leachability and biocompatibility (haemolytic potential, thrombogenicity and cytotoxicity). A conventional organic plasticizer (di-isononyl phthalate) was used for comparison purposes. The results obtained showed that it was possible to change the neat PVC hydrophobicity, and consequently its water uptake capacity and plasticizer leachability, just by changing the PhIL employed and its composition. It was also possible to significantly change the thermal and mechanical properties of PVC films by choosing appropriate PhIL cation/anion combinations. However, a specific PhIL may not always be capable of simultaneously keeping and/or improving both physical properties. In addition, ionic halide salts were found to promote PVC dehydrochlorination. Finally, none of the prepared materials presented toxicity against Caco-2 cells, though pure [P(6,6,6,14)][dca] decreased HepG2 cells viability. Moreover, PVC films with [P(6,6,6,14)][dca] and [P(4,4,4,4)][Cl] were found to be haemolytic and thus these PhILs must be avoided as PVC modifiers if biomedical applications are envisaged. In conclusion, from all the PhILs tested, [P(6,6,6,14)][Tf(2)N] showed the most promising results regarding blood compatibility, leaching and permeability to gases of PVC films. The results presented are a strong indicator that adequate PhILs may be successfully employed as PVC multi-functional plasticizers for a wide range of potential applications, including those in the biomedical field.

Solubility of coenzyme Q10 in supercritical carbon dioxide

Abstract The equilibrium solubility of coenzyme Q10 (CoQ10) in supercritical carbon dioxide (scCO2) was measured by a static analytical method in the pressure range from 9 to 26 MPa, at temperatures of 305, 313 and 323 K. The cosolvent effect of ethanol in the solubility of the bioactive compound in scCO2 has been investigated, at 15 MPa and 313 K. A preliminary study of the viability of extracting CoQ10 with scCO2 has been investigated at 15 MPa and 313 K, using the content of commercial pharmaceutical capsules as the solid matrix feed. The solubility data results were correlated by use of the empirical density-based Chrastil model.

Pre-treatment and extraction techniques for recovery of added value compounds from wastes throughout the agri-food chain

The enormous quantity of food wastes discarded annually forces a look into alternatives for this interesting feedstock. Thus, food bio-waste valorisation is one of the current imperatives of society. This review is the most comprehensive overview of currently existing technologies and processes in this field. It tackles classical and innovative physical, physico-chemical and chemical methods of food waste pre-treatment and extraction for the recovery of added value compounds and detection by modern technologies and is an outcome of the COST Action EUBIS, TD1203 Food Waste Valorisation for Sustainable Chemicals, Materials and Fuels.

Cholinium-based ionic liquids with pharmaceutically active anions

Novel ionic liquids (ILs) containing cholinium as a benign cation combined with anions based on five active pharmaceutical ingredients (APIs), namely, nalidixic acid, niflumic acid, 4-amino-salicylic acid, pyrazinoic acid and picolinic acid, were prepared via a simple and sustainable two-step anion exchange reaction. The solubility of the prepared pharmaceutically active ILs (API-ILs) in both water and simulated biological fluids at 25 °C and 37 °C, as well as the solubility of the parent APIs, were measured. Further, in vitro cytotoxicity levels for both cholinium-based API-ILs and parent APIs were established using two different human cells lines, namely Caco-2 colon carcinoma cells and HepG2 hepatocellular carcinoma cells. Herein, the dual nature of ILs is exploited by combining the cheap, available and essential nutrient cholinium cation with pharmaceutically active anions, upgrading the chemical, physical and biopharmaceutical properties, particularly melting point, aqueous solubility and the potential to penetrate cell membranes of the parent APIs, without impair their cytotoxicity response which prompt opportunities for creating further advances in pharmaceutical challenges.

Alginate-based hybrid aerogel microparticles for mucosal drug delivery

The application of biopolymer aerogels as drug delivery systems (DDS) has gained increased interest during the last decade since these structures have large surface area and accessible pores allowing for high drug loadings. Being biocompatible, biodegradable and presenting low toxicity, polysaccharide-based aerogels are an attractive carrier to be applied in pharmaceutical industry. Moreover, some polysaccharides (e.g. alginate and chitosan) present mucoadhesive properties, an important feature for mucosal drug delivery. This feature allows to extend the contact of DDS with biological membranes, thereby increasing the absorption of drugs through the mucosa. Alginate-based hybrid aerogels in the form of microparticles (<50μm) were investigated in this work as carriers for mucosal administration of drugs. Low methoxyl pectin and κ-carrageenan were co-gelled with alginate and further dried with supercritical CO2 (sc-CO2). Spherical mesoporous aerogel microparticles were obtained for alginate, hybrid alginate/pectin and alginate/κ-carrageenan aerogels, presenting high specific surface area (370-548m(2)g(-1)) and mucoadhesive properties. The microparticles were loaded with ketoprofen via adsorption from its solution in sc-CO2, and with quercetin via supercritical anti-solvent precipitation. Loading of ketoprofen was in the range between 17 and 22wt% whereas quercetin demonstrated loadings of 3.1-5.4wt%. Both the drugs were present in amorphous state. Loading procedure allowed the preservation of antioxidant activity of quercetin. Release of both drugs from alginate/κ-carrageenan aerogel was slightly faster compared to alginate/pectin. The results indicate that alginate-based aerogel microparticles can be viewed as promising matrices for mucosal drug delivery applications.

Portuguese winemaking residues as a potential source of natural anti-adenoviral agents

Abstract To date there are no licensed systemic or topical treatments in Europe or the USA for adenovirus infections. In the present paper, we evaluate the effect of a polyphenol-based grape extract (NE) obtained from Portuguese white-winemaking by-products, and Resveratrol in pure form, on adenovirus type 5 infection. For this purpose, recombinant adenovirus vectors (Ad-5) and a human-derived cell line (293) were used as models. The NE and Resveratrol at the used concentrations do not induce cell cytotoxicity or direct virucidal activity; however, they reduce 4.5 and 6.5 log (TCID50/ml) on total infectious Ad-5 production, respectively. The capacity of Ad-5 replication upon removal of NE and Resveratrol after 24 h post infection was also evaluated. In contrast to Resveratrol, the highest evaluated NE concentration inhibits irreversibly the Ad-5 replication. These results provide useful information for the use of NE and Resveratrol as potential sources of promising natural antiviral agents on Ad-5 infection.

Development of multicore hybrid particles for drug delivery through the precipitation of CO2 saturated emulsions.

Hybrid lipid-polymer particles are gaining increasing interest to be applied as drug delivery systems due to their greater stability in biological fluids and enhanced cellular uptake of drugs. However, a major drawback is the fact that these particles are usually produced through techniques that use organic solvents. This work studies the possibility of producing for the first time hybrid particles composed by lipid multicores enveloped in a polymeric layer through Particles from Gas Saturated Solutions (PGSS(®)), without using organic solvents. An oil-in-water emulsion, composed by Gelucire 43/01™ (GEL) as the discontinuous phase and by an aqueous polyethylene glycol 4000 (PEG) solution as the continuous phase, was successfully precipitated by PGSS(®). Operating conditions that ensured the stability of the CO2 saturated emulsion were previously evaluated. The resulting PEG-GEL particles present a spherical-like morphology constituted by several lipid cores encapsulated into a polymeric shell. The applicability of these structured particles to be used as drug delivery system (DDS) was studied by using ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID), as model drug. The particles provided an initial burst release of the drug due to the progressive dissolution of the external layer of PEG, followed by a controlled release of the NSAID from the GEL cores.

Protective Effect of a (Poly)phenol-Rich Extract Derived from Sweet Cherries Culls against Oxidative Cell Damage

Oxidative stress is one of the key phenomena behind the most common types of chronic diseases. Therefore, the modulation of oxidative stress is an interesting target for acting either through prevention or as a therapeutic approach. In this work, a Portuguese variety of cherry (Saco Cherry) was processed in order to obtain a potent in vitro antioxidant phenolic-rich extract (Ch-PRE), which was further explored to evaluate its potential application as nutraceutical agent against cellular oxidative stress damage. Ch-PRE was mainly composed of anthocyanins, particularly cyanidin-3-rutinoside, cyanidin-3-glucoside, peonidin-3-glucoside and neochlorogenic acid, and exhibited a potent chemical antioxidant activity expressed by its oxygen radical absorbance capacity (ORAC) and hydroxyl radical averting capacity (HORAC) values. Ch-PRE also displayed effective intracellular radical scavenging properties in intestinal epithelial and neuronal cells challenged with oxidative stress but showed a different order of effectiveness regarding the modulation of endogenous antioxidant system. Ch-PRE could be an attractive candidate to formulate an agent for the prevention of oxidative stress-induced disorders such as intestinal inflammation disorders or with an appropriated delivery system for neurodegenerative diseases.