Carla S. M. Pereira

Ethyl lactate as a solvent: Properties, applications and production processes – a review

Ethyl lactate is an environmentally benign solvent with effectiveness comparable to petroleum-based solvents. The worldwide solvent market is about 30 million pounds per year, where ethyl lactate can have an important share. It is considered a chemical commodity and has attracted much attention in recent years, since it is formed by the esterification reaction of ethanol and lactic acid, which can be generated from biomass raw materials through fermentation. In this work, an overview regarding the main properties and applications of ethyl lactate, as well as its synthesis and production processes, with a particular emphasis on reactive/separation processes, is presented.

Polymer-based nanoparticles for oral insulin delivery: Revisited approaches

Diabetes mellitus is a high prevalence and one of the most severe and lethal diseases in the world. Insulin is commonly used to treat diabetes in order to give patients a better life condition. However, due to bioavailability problems, the most common route of insulin administration is the subcutaneous route, which may present patients compliance problems to treatment. The oral administration is thus considered the most convenient alternative to deliver insulin, but it faces important challenges. The low stability of insulin in the gastrointestinal tract and low intestinal permeation, are problems to overcome. Therefore, the encapsulation of insulin into polymer-based nanoparticles is presented as a good strategy to improve insulin oral bioavailability. In the last years, different strategies and polymers have been used to encapsulate insulin and deliver it orally. Polymers with distinct properties from natural or synthetic sources have been used to achieve this aim, and among them may be found chitosan, dextran, alginate, poly(γ-glutamic acid), hyaluronic acid, poly(lactic acid), poly(lactide-co-glycolic acid), polycaprolactone (PCL), acrylic polymers and polyallylamine. Promising studies have been developed and positive results were obtained, but there is not a polymeric-based nanoparticle system to deliver insulin orally available in the market yet. There is also a lack of long term toxicity studies about the safety of the developed carriers. Thus, the aims of this review are first to provide a deep understanding on the oral delivery of insulin and the possible routes for its uptake, and then to overview the evolution of this field in the last years of research of insulin-loaded polymer-based nanoparticles in the academic and industrial fields. Toxicity concerns of the discussed nanocarriers are also addressed.

Improving the quality of collaboration requirements for information management through social networks analysis

The right choice of the method of organizational analysis to use is a key factor in the process of requirements analysis and specification of an information system. Although a high number of approaches of organizational analysis exist, the choice of the most appropriate option for each concrete case will influence the quality of the results obtained in the analysis of requirements and consequent specification. This paper presents a new way for organizational analysis to improve the quality of the requirements of systems that support information management and where collaboration is an important aspect. This is achieved through the application of the social network analysis approach, applied to refine, classify and prioritize the requirements for collaboration and information management in an organization. The paper begins by analysing shortly content management systems and wiki systems as IT platforms for collaboration and information management. After having described the method, a practical case of application of SNetCol method to an R&D institution is presented. The paper finishes by presenting the results of the evaluation of the two particular technological options considered for satisfying the specified requirements are described.

Fixed Bed Adsorptive Reactor for Ethyl Lactate Synthesis: Experiments, Modelling, and Simulation

Abstract Multicomponent adsorption equilibrium data were measured through binary adsorption experiments performed in a fixed bed column packed with Amberlyst 15-wet for the ethyl lactate system, at 20°C and 50°C. A novel approach based on the multicomponent Langmuir isotherm was used assuming a constant monolayer capacity in terms of volume for all species, reducing the adjustable parameters from 8 to 5, for each temperature. Reactive adsorption experiments were performed and used to validate a mathematical model developed for both fixed bed and simulated moving bed reactors, which involves velocity variations due to the change of multicomponent mixture properties.

Dissecting stromal-epithelial interactions in a 3D in vitro cellularized intestinal model for permeability studies

Absorption evaluation plays an increasingly important role at the early stage of drug discovery due to its potential to scan the ADME (absorption, distribution, metabolism and excretion) properties of new drug candidates. Therefore, a new three-dimensional (3D) inxa0vitro model replicating the intestinal functioning is herein proposed aiming to dissect the stromal-epithelial interactions and evaluate the permeation of a model drug, insulin. Inspired on the intestinal mucosal architecture, the present model comprises intestinal myofibroblasts (CCD18-Co cells) embedded in Matrigel, onto which epithelial enterocytes (Caco-2 cells) and mucus-producing cells (HT29-MTX cells) were seeded. CCD18-Co myofibroblasts showed to have a central role in the remodeling of the surrounding matrix confirmed by the production of fibronectin. Subsequently, this matrix revealed to be essential to the maintenance of the model architecture by supporting the overlying epithelial cells. In terms of functionality, this model allowed the efficient prediction of insulin permeability in which the presence of mucus, the less tight character between Caco-2 and HT29-MTX epithelial cells and the 3D assembly were critical factors. Concluding, this model constitutes a robust tool in the drug development field with potential to bridge the traditional 2D cell culture models and inxa0vivo animal models.

Supporting conceptualisation processes in collaborative networks: a case study on an R&D project

The development of new products or processes involves the creation, re-creation and integration of conceptual models from the related scientific and technical domains. Particularly, in the context of collaborative networks of organisations (CNO) (e.g. a multi-partner, international project) such developments can be seriously hindered by conceptual misunderstandings and misalignments, resulting from participants with different backgrounds or organisational cultures, for example. The research described in this article addresses this problem by proposing a method and the tools to support the collaborative development of shared conceptualisations in the context of a collaborative network of organisations. The theoretical model is based on a socio-semantic perspective, while the method is inspired by the conceptual integration theory from the cognitive semantics field. The modelling environment is built upon a semantic wiki platform. The majority of the article is devoted to developing an informal ontology in the context of a European R&D project, studied using action research. The case study results validated the logical structure of the method and showed the utility of the method.

In vitro M-like cells genesis through a tissue-engineered triple-culture intestinal model

Although fewer in number, M-cells are considered antigen sampling cells, acting as a gateway for antigens from the gut lumen and presenting an impressive aptitude for particle transcytosis. These features make M-cells attractive targets for oral drug delivery studies, but this has been poorly explored. New and reproducible tissue-like in vitro models for studying intestinal sampling and permeability mechanisms are needed. The combination of different cell players in such models offers improved microenvironments with higher physiologic relevance. Here, a tissue-engineered model was established, by co-culturing Caco-2 absorptive cells, HT29-MTX mucus-producing cells and Raji B lymphocytes. After 3 weeks of cell co-culture, the presence of M-like cells was evidenced by the loss of brush-border organization, detected by the lack of microvilli. The triple-culture model showed to be efficient for insulin transport, a process that was influenced by the tightness of junctions between epithelial cells and the presence of mucus and M-like cells. Ultimately, the proposed tissue-engineered model provides a more complete and reliable tool to perform drug permeability tests, as compared to traditional models, and may also find applicability as an in vitro system to study transdifferentiation mechanisms of M cells.

Chromatographic separation of prebiotic oligosaccharides. Case study: separation of galacto-oligosaccharides on a cation exchanger

Chromatographic separation of prebiotic oligosaccharides, galacto-oligosaccharides from a typical post-reaction mixture containing unreacted substrate lactose and by-products glucose and galactose was investigated. A commercial cation-exchange resin Dowex 50WX4 was chosen as a prospective preparative-scale adsorbent and separation performance of its four ionic forms, H+, Na+, K+ and Ca2+, was tested. Since adsorption equilibrium isotherms were linear within the entire investigated range of concentrations, they were determined by pulse experiments for all saccharides present in a typical post reaction mixture including tri- and tetragalacto-oligosaccharides. From the four counter ions listed above, hydrogen offered the best selectivity and column performance. The selected H+-form of the cation exchanger was further investigated by means of frontal analysis where high ionic strength and elevated viscosity appear and can play a substantial role. Breakthrough curves were measured for monosaccharides, lactose, glucose–lactose mixture and a multicomponent commercial mixture of galacto-oligosaccharides, Vivinal® GOS. The breakthrough curves were successfully described by the dispersive plug flow model with linear driving force approximation.

Cell-based in vitro models for intestinal permeability studies

Among all the delivery routes for drug administration, the oral route is undoubtedly the preferred one. However, despite the continuous advances in the pharmaceutical industry, oral administration of drugs is still a huge challenge because of the harsh conditions of the gastrointestinal tract. Suitable methods, introduced in an early stage of drug design and development, that allow researchers to foresee the permeability behavior of those drugs are essential to improve the drug delivery field. The Caco-2 model has been the gold-standard in vitro method used for such purposes. However, it is far from being a perfect model because of its lack of many important players that interfere in drug absorption mechanisms. Improvements were introduced to the model with the addition of other cell lines, such as HT29-MTX cells, Raji B cells, and fibroblasts. In order to mimic more closely the complexity of the human intestine, tridimensional models have been developed in the past few years, filling the gap between in vivo models. In this review, the intestinal in vitro models are described, addressing their main advantages and drawbacks as well as the conditions to establish each model.

Chromatographic Separation of Isomaltooligosaccharides on Ion-Exchange Resins: Effect of the Cationic Form

Prebiotic isomaltooligosaccharides (IMOs) are composed of α-d-glucose units linked by glucosidic α (1Ø6) bonds and they remain intact until reaching the large bowels, where they are metabolized by bifidobacteria and lactobacillus. These saccharides can also be synthesized enzymatically, wherein the reaction media is composed of monosaccharides (glucose and fructose), disaccharides (sucrose and maltose), IMOs (the product of interest) and dextrans. Dextrans are readily separated by solvent precipitation; however, continuous chromatographic separation (simulated moving bed or SMB) should be an interesting option for the enrichment and purification of IMOs from mono- and disaccharides. The objective of the present work was to measure fundamental adsorption data of IMOs, mono- and disaccharides in preparative columns packed with ion-exchange resin of different cationic forms (K+, Ca+, H+ and Na+), so as to verify the influence of the cation on the selectivity and capacity. Ion exchange in H+ form showed the best performance in terms of selectivity between maltose and maltotriose, but the resin in the K+ form had superior adsorption capacities. Additionally, on the basis of equilibrium theory, optimal SMB operating conditions for resin H+ will yield the highest productivity as compared with the other cationic forms.