PLGA Based Drug Carrier and Pharmaceutical Applications: The Most Recent Advances

Poly(lactic-co-glycolic acid) (PLGA) is one of the most successful polymers that has been used to produce medicines, such as drug carriers (DC) [...]</jats:p

Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohorts

We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.(SFRH/BPD/115169/2016) funded by Fundação para a Ciência e Tecnologia (FCT); ERDF (European Regional Development Fund) through the operations: POCI-01-0145-FEDER-029130 ('mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases—generalisation and evaluation of gamification, peer support and advanced image processing technologies') cofunded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).info:eu-repo/semantics/publishedVersio

Fluorinated Molecules and Nanotechnology: Future 'Avengers' against the Alzheimer's Disease?

Alzheimer's disease (AD) is a serious health concern, affecting millions of people globally, which leads to cognitive impairment, dementia, and inevitable death. There is still no medically accepted treatment for AD. Developing therapeutic treatments for AD is an overwhelming challenge in the medicinal field, as the exact mechanics underlying its devastating symptoms is still not completely understood. Rather than the unknown mechanism of the disease, one of the limiting factors in developing new drugs for AD is the blood-brain barrier (BBB). A combination of nanotechnology with fluorinated molecules is proposed as a promising therapeutic treatment to meet the desired pharmacokinetic/physiochemical properties for crossing the BBB passage. This paper reviews the research conducted on fluorine-containing compounds and fluorinated nanoparticles (NPs) that have been designed and tested for the inhibition of amyloid-beta (A beta) peptide aggregation. Additionally, this study summarizes fluorinated molecules and NPs as promising agents and further future work is encouraged to be effective for the treatment of AD

Metal alloys, matrix inclusions and manufacturing techniques of Moinhos de Golas collection (North Portugal): a study by micro-EDXRF, SEM–EDS, optical microscopy and X-ray radiography

"Article:820"A collection of 35 metallic artefacts comprising various typologies, some of which can be attributed to the Bronze Age and others to later periods, were studied to provide detailed information on elemental composition, manufacturing techniques and preservation state. Elemental analysis by micro-EDXRF and SEM–EDS was performed to investigate the use of different alloys and to study the presence of microstructural heterogeneities, as inclusions. X-ray radiography, optical microscopy and SEM–EDS were used to investigate manufacturing techniques and degradation features. Results showed that most of the artefacts were produced in a binary bronze alloy (Cu–Sn) with 10–15 wt% Sn and a low concentration of impurities. Other artefacts were produced in copper or in brass, the latest with varying contents of Zn, Sn and Pb. A variety of inclusions in the metal matrices were also found, some related to specific types of alloys, as (Cu–Ni)S2 in coppers, or ZnS in brasses. Microstructural observations revealed that the majority of the artefacts were subjected to cycles of thermomechanical processing after casting, being evident that among some artefacts different parts were subjected to distinct treatments. The radiographic images revealed structural heterogeneities related to local corrosion processes and fissures that seem to have developed in wear-tension zones, as in the handle of some daggers. Radiographic images were also useful to detect the use of different materials in one particular brass artefact, revealing the presence of a possible Cu–Sn solder.This work was funded by FEDER funds through the COMPETE 2020 Programme and National Funds through FCT— Fundação para a Ciência e a Tecnologia under the project UID/CTM/ 50025/2013 to CENIMAT/I3N. C2 TN/IST authors gratefully acknowledge the FCT support through the UID/Multi/04349/2013 project. EF acknowledges FCT for the grant SFRH/BPD/97360/2013. JF acknowledge FCT for the grant SFRH/BD/65143/2009. Part of this project has been done in the framework of the FCT project ENARDAS (PTDC/HISARQ/112983/2009).info:eu-repo/semantics/publishedVersio

The potential effect of fluorinated compounds in the treatment of Alzheimer's disease

Drug development for neurodegenerative diseases such as Alzheimer's disease (AD) is a challenge, not only due to the cellular molecular mechanisms involved, but also because of the inherent difficulty of most molecules to cross the blood-brain-barrier (BBB). A promising approach to overcome these drawbacks is developing fluorinated molecules and supramolecular assemblies. This review focuses on the therapeutic potential of new fluorinated molecules, developed as active and selective agents for AD, to meet the desired pharmacokinetic/pharmacodynamic properties and BBB targeting. The methods to fluorinate organic molecules and a brief characterization of the mechanisms of AD progression and therapeutic approaches are described

Factorial design as a tool for the optimization of plga nanoparticles for the co-delivery of temozolomide and o6-benzylguanine

Poly(D,L-lactic-co-glycolic) (PLGA) nanoparticles (NPs) have been widely studied for several applications due to their advantageous properties, such as biocompatibility and biodegradability. Therefore, these nanocarriers could be a suitable approach for glioblastoma multiforme (GBM) therapy. The treatment of this type of tumours remains a challenge due to intrinsic resistance mechanisms. Thus, new approaches must be envisaged to target GBM tumour cells potentially providing an efficient treatment. Co-delivery of temozolomide (TMZ) and O6-benzylguanine (O6BG), an inhibitor of DNA repair, could provide good therapeutic outcomes. In this work, a fractional factorial design (FFD) was employed to produce an optimal PLGA-based nanoformulation for the co-loading of both molecules, using a reduced number of observations. The developed NPs exhibited optimal physicochemical properties for brain delivery (dimensions below 200 nm and negative zeta potential), high encapsulation efficiencies (EE) for both drugs, and showed a sustained drug release for several days. Therefore, the use of an FFD allowed for the development of a nanoformulation with optimal properties for the co-delivery of TMZ and O6BG to the brain

Molecular interactions between Vitamin B12 and membrane models: A biophysical study for new insights into the bioavailability of Vitamin

Vitamin B12 (VB12) deficiency is one of the most common malnutrition problems worldwide and is related to its poor bioavailability. The lipid composition of cell membranes and molecule-cell membrane lipid interactions are major factors affecting the bioavailability of nutrients. So, the study of these interactions may allow predicting the behavior of VB12 at cellular membranes and the effects on its activity. Thus, lipid vesicles with lipid composition similar to the majority of eukaryotic cell membranes were used as biomembrane models, and their interactions with VB12 molecules were evaluated. For that, different parameters were assessed such as the lipophilicity of VB12, its preferential location in the membrane and its effect on the physical properties of the bilayer. VB12 showed high affinity for the biological membranes, not inducing any biophysical changes in their properties. The interactions of VB12 with the membrane was affected by the complexity of the bilayer, since its increase in order and rigidity hinders the diffusion of molecules. Thus, the low bioavailability of VB12 is not related with its interactions with the biological membranes. (c) 2020 Elsevier B.V

Effect of invader removal: pollinators stay but some native plants miss their new friend

Removal of invasive species often benefits biological diversity allowing ecosystems’ recovery. However, it is important to assess the functional roles that invaders may have established in their new areas to avoid unexpected results from species elimination. Invasive animal-pollinated plants may affect the plant–pollination interactions by changing pollinator availability and/or behaviour in the community. Thus, removal of an invasive plant may have important effects on pollinator community that may then be reflected positive or negatively on the reproductive success of native plants. The objective of this study was to assess the effect of removing Oxalis pescaprae, an invasive weed widely spread in the Mediterranean basin, on plant–pollinator interactions and on the reproductive success of co-flowering native plants. For this, a disturbed area in central Portugal, where this species is highly abundant, was selected. Visitation rates, natural pollen loads, pollen tube growth and natural fruit set of native plants were compared in the presence of O. pes-caprae and after manual removal of their flowers. Our results showed a highly resilient pollination network but also revealed some facilitative effects of O. pes-caprae on the reproductive success of co-flowering native plants. Reproductive success of the native plants seems to depend not only on the number and diversity of floral visitors, but also on their efficiency as pollinators. The information provided on the effects of invasive species on the sexual reproductive success of natives is essential for adequate management of invaded areas.This work is financed by FEDER funds through the COMPETE Program and by Portuguese Foundation for Science and Technology (FCT) funds in the ambit of the project PTDC/ BIA-BIC/110824/2009, by CRUP Acc¸o˜es Integradas Luso- Espanholas 2010 with the project E10/10, by MCI-Programa de Internacionalizacio´n de la I ? D (PT2009-0068) and by the Spanish DGICYT (CGL2009-10466), FEDER funds from the European Union, and the Xunta de Galicia (INCITE09- 3103009PR). FCT also supported the work of S. Castro (FCT/ BPD/41200/2007) and J. Costa (CB/C05/2009/209; PTDC/ BIA-BIC/110824/2009). The work of V. Ferrero was supported by the Fundacio´n Ramo´n Areces

Enhancing cannabidiol bioaccessibility using ionic liquid as emulsifier to produce nanosystems: Characterization of structures, cytotoxicity assessment, and in vitro digestion

The emulsifying potential of a biocompatible ionic liquid (IL) to produce lipid-based nanosystems developed to enhance the bioaccessibility of cannabidiol (CBD) was investigated. The IL (cholinium oleate) was evaluated at concentrations of 1 % and 2 % to produce nanoemulsions (NE-IL) and nanostructured lipid carriers (NLC-IL) loaded with CBD. The IL concentration of 1 % demonstrated to be sufficient to produce both NE-IL and NLC-IL with excellent stability properties, entrapment efficiency superior to 99 %, and CBD retention rate of 100 % during the storage period evaluated (i.e. 28 days at 25 °C). The in vitro digestion evaluation demonstrated that the NLC-IL provided a higher stability to the CBD, while the NE-IL improved the CBD bioaccessibility, which was mainly related to the composition of the lipid matrices used to obtain each nanosystem. Finally, it was observed that the CBD cytotoxicity was reduced when the compound was entrapped into both nanosystems.info:eu-repo/semantics/publishedVersio

RVG29-Functionalized Lipid Nanoparticles for Quercetin Brain Delivery and Alzheimers Disease

Purpose: Lipid nanoparticles (SLN and NLC) were functionalized with the RVG29 peptide in order to target the brain and increase the neuronal uptake through the nicotinic acetylcholine receptors. These nanosystems were loaded with quercetin to take advantage of its neuroprotective properties mainly for Alzheimer's disease. Methods: The functionalization of nanoparticles with RVG29 peptide was confirmed by NMR and FTIR. Their morphology was assessed by transmission electron microscopy and nanoparticles size, polydispersity and zeta potential were determined by dynamic light scattering. The in vitro validation tests were conducted in hCMEC/D3 cells, a human blood-brain barrier model and thioflavin T binding assay was conducted to assess the process of amyloid-beta peptide fibrillation typical of Alzheimer's disease. Results: RVG29-nanoparticles displayed spherical morphology and size below 250 nm, which is compatible with brain applications. Zeta potential values were between −20 and −25 mV. Quercetin entrapment efficiency was generally higher than 80% and NLC nanoparticles were able to encapsulate up to 90%. The LDH assay showed that there is no cytotoxicity in hCMEC/D3 cell line and RVG29-nanoparticles clearly increased in 1.5-fold the permeability across the in vitro model of blood-brain barrier after 4 h of incubation compared with non-functionalized nanoparticles. Finally, this nanosystem was capable of inhibiting amyloid-beta aggregation in thioflavin T binding assay, suggesting its great potential for neuroprotection. Conclusions: RVG29-nanoparticles that simultaneously target the blood-brain barrier and induce neurons protection against amyloid-beta fibrillation proved to be an efficient way of quercetin delivery and a promising strategy for future approaches in Alzheimer's disease. [Figure not available: see fulltext.]. (c) 2020, Springer Science+Business Media, LLC, part of Springer Nature