An insight on lipid nanoparticles for therapeutic proteins delivery

Therapeutic proteins are well-tolerated bioactive compounds used in different therapies, due to its high speci-ficity and biopotency. Nevertheless, they may also present some physicochemical instability, leading to loss of bioactivity hampering treatments. This can be avoided by its loading into lipid nanoparticles, which are biocompatible and biodegradable carriers. The use of lipids nanoparticles to deliver therapeutic proteins over-comes different challenges, allowing its administration by all delivery routes. Thus, therapeutic proteins may be loaded into liposomes, the first developed lipid-based nanocarriers composed of phospholipid bilayers, solid lipid nanoparticles composed of a solid lipid matrix, or nanostructured lipid carriers made of a blend of liquid and solid lipid as matrix. The latter are currently marking the trend in lipid nanocarriers due to its high loading capacity, good stability upon storage and better sustained release pattern. Production methods must focus both on attaining the desired nanocarrier features, and maintenance of therapeutic proteins structure and bioactivity. This review aims to make an insight overview on the application of lipid nanoparticles to deliver therapeutic proteins, showing its potential in different therapies. A special focus is given to the production techniques to obtain therapeutic proteins-loaded lipid nanoparticles.info:eu-repo/semantics/publishedVersio

Ancient tin production: Slags from the Iron Age Carvalhelhos hillfort (NW Iberian Peninsula)

Provenance and production of tin in the Ancient World has since long been a major topic of discussion among archaeologists. In Western Europe, where significant tin ore (cassiterite) deposits are known, only a few remains of ancient tin production, such as tin slags, have been detected. In the present work, elemental and microstructural analyses by WDXRF, SEM-EDS and XRD were performed on recently recognised tin slags from the Iron Age Carvalhelhos hillfort located in NW Iberia, a territory that represents the largest extension with tin mineralisation in Western Europe. Elemental and microstructural characterisation of cassiterite collected in a pilot field survey in the region of the hillfort are presented and discussed, as well as two ceramic fragments that could be part of a smelting structure and an iron slag from the settlement. Results show that the tin slags have variable but high contents in Sn, similarly to Pre-Medieval tin slags found in other Western European areas, but also high contents of Ta and Nb, which specifically distinguish them from other tin slags, such as those found in SW Britain. Tin ores from the hillfort region frequently have Ta and Nb in cassiterite solid solution or as inclusions of columbite group minerals, relating well with the Carvalhelhos tin slags. Up to present, the Carvalhelhos slags are amongst the very few ancient tin slags known in Western Europe, and their study can contribute to a better knowledge on ancient tin sources and trade routes

Analysis of spinning reserves in systems with variable power sources

In this paper is studied an approach based on risk assessment to solve the scheduling of a power production system with variable power sources. The spinning reserves resulting from the unit commitment are analyzed too. In this methodology there are no infeasible solutions, only more or less costly solutions associated to the operation risks, such as, load or renewable production curtailment. The uncertainty of forecasted production and load demand are defined by probability distribution functions. The methodology is tested in a real case study, an island with high penetration of renewable power production. Finally, forecasted and measured reserves are compared, once the reserves are strongly linked with the forecasting quality. The results of a real case study are presented and discussed. They show the difficulty to achieve complete robust solutions.info:eu-repo/semantics/publishedVersio

The impact of Flavonoid-Loaded nanoparticles in the UV protection and safety profile of topical sunscreens

Excessive UV radiation exposure is harmful to skin cells since sunburn is accompanied by oxidative burst, leading to a rapid increase in skin cancer. However, the insufficient UV photoprotection of approved sunscreens and the negative impact of their compositions on ecosystems and human health makes the utility of sunscreen a questionable recommendation. Therefore, discovering UV filters with significant antioxidant activity and improved topical performance and photostability is an urgent need. Recently, the use of nanosized natural molecules incorporated in sunscreens has been a scientific hot topic, as it has been suggested that they provide a synergistic effect with synthetic UV filters, improving overall SPF and antioxidant activity, higher retention on the epidermis, and less toxicity. The aim of this review was to verify the usefulness of sunscreens incorporating flavonoid-loaded nanoparticles. A literature review was performed, where original and review articles published in the last 6 years were analyzed. Formulations containing nanosized flavonoids with improved UVA photoprotection and safer toxicological profiles, associated or not with synthetic filters, are promising sunscreens and more clinical investigation must be performed to validate these findings.LA/P/0101/2020; LA/P/0140/2020info:eu-repo/semantics/publishedVersio

Insights into nanomedicine for head and neck cancer diagnosis and treatment

Head and neck cancers rank sixth among the most common cancers today, and the survival rate has remained virtually unchanged over the past 25 years, due to late diagnosis and ineffective treatments. They have two main risk factors, tobacco and alcohol, and human papillomavirus infection is a secondary risk factor. These cancers affect areas of the body that are fundamental for the five senses. Therefore, it is necessary to treat them effectively and non-invasively as early as possible, in order to do not compromise vital functions, which is not always possible with conventional treatments (chemotherapy or radiotherapy). In this sense, nanomedicine plays a key role in the treatment and diagnosis of head and neck cancers. Nanomedicine involves using nanocarriers to deliver drugs to sites of action and reducing the necessary doses and possible side effects. The main purpose of this review is to give an overview of the applications of nanocarrier systems to the diagnosis and treatment of head and neck cancer. Herein, several types of delivery strategies, radiation enhancement, inside-out hyperthermia, and theragnostic approaches are addressed.info:eu-repo/semantics/publishedVersio

Edible films as oral delivery systems for xanthines extracted from medicinal plants: an experimental design approach

Two formulations of edible films intended for oral delivery of therapeutic xanthines were developed, following an experimental design approach. Gelatin type A and sodium carboxymethylcellulose were used as polymeric matrices with different physico-chemical nature. Caffeine, a well-known methylxhanthine, was used as model bioactive molecule, representing overall xanthines (e.g. caffeine, theophylline, theobromine) extracted from medicinal plants. Fourier-transform infrared spectroscopy (FTIR) analysis was performed to outwit the formation of covalent bonds between caffeine and the matrix of edible films. Scanning electron microscopy (SEM) was performed to assess if caffeine was homogeneously dispersed on the matrix of edible films. Simulation of gastrointestinal tract and ex vivo permeability studies across intestinal mucosa were performed to predict the delivery profile of caffeine from developed formulations of edible films. Gelatin type A-based edible films offered a slow release of caffeine whereas sodium carboxymethylcellulose-based edible films promote an immediate release of caffeine.info:eu-repo/semantics/publishedVersio

Anticancer activity of rutin and its combination with ionic liquids on renal cells

The renal cell carcinoma (RCC) is the most common type of kidney cancer. Identifying novel and more effective therapies, while minimizing toxicity, continues to be fundamental in curtailing RCC. Rutin, a bioflavonoid widely found in nature, has shown promising anticancer properties, but with limited applicability due to its poor water solubility and pharmacokinetics. Thus, the potential anticancer effects of rutin toward a human renal cancer cell line (786-O), while considering its safety in Vero kidney cells, was assessed, as well as the applicability of ionic liquids (ILs) to improve drug delivery. Rutin (up to 50 µM) did not show relevant cytotoxic effects in Vero cells. However, in 786-O cells, a significant decrease in cell viability was already observed at 50 µM. Moreover, exposure to rutin caused a significant increase in the sub-G1 population of 786-O cells, reinforcing the possible anticancer activity of this biomolecule. Two choline-amino acid ILs, at non-toxic concentrations, enhanced rutin's solubility/loading while allowing the maintenance of rutin's anticancer effects. Globally, our findings suggest that rutin may have a beneficial impact against RCC and that its combination with ILs ensures that this poorly soluble drug is successfully incorporated into ILs-nanoparticles hybrid systems, allowing controlled drug delivery.Fundação para a Ciência e Tecnologia (FCT, Portugal): UID/DTP/04567/2019/ UIDB/00100/2020/ UIDB/04565/2020. ALIES grant PADDIC 2018-2019info:eu-repo/semantics/publishedVersio

Nanocarrier-mediated topical insulin delivery for wound healing

Wound care has been clinically demanding due to inefficacious treatment that represents an economic burden for healthcare systems. In Europe, approximately 7 million people are diagnosed with untreated wounds, leading to a cost between 6.000€ and 10.000€ per patient/year. In the United States of America, 1.5 million people over 65 years old suffer from chronic wounds. A promising therapeutic strategy is the use of exogenous growth factors because they are decreased at the wound site, limiting the recovery of the skin. Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. The aim of this review is to perform a standing point about a promising strategy to treat different types of wounds by the topical delivery of insulin-loaded nanocarriers.FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operational Programme for Competitiveness and Internationalization(POCI) POCI-01-0145-FEDER-032610, PTDC/MEC-DER/32610/2017, UIDB/50006/2020, UIDB/04326/2020, UIDB/04565/2020info:eu-repo/semantics/publishedVersio

Plagiarism detection: A tool survey and comparison

We illustrate the state of the art in software plagiarism detection tools by comparing their features and testing them against a wide range of source codes. The source codes were edited according to several types of plagiarism to show the tools accuracy at detecting each type. The decision to focus our research on plagiarism of programming languages is two fold: on one hand, it is a challenging case-study since programming languages impose a structured writing style; on the other hand, we are looking for the integration of such a tool in an Automatic-Grading System (AGS) developed to support teachers in the context of Programming courses. Besides the systematic characterisation of the underlying problem domain, the tools were surveyed with the objective of identifying the most successful approach in order to design the aimed plugin for our AGS.(undefined