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Polymersomes, self-assembled nanoparticles composed of amphiphilic block copolymers, have emerged as promising versatile nanovesicles with various applications, such as drug delivery, medical imaging, and diagnostics. The integration of click chemistry reactions, specifically the copper [I]-catalysed azide–alkyne cycloaddition (CuAAC), has greatly expanded the functionalisation and bioconjugation capabilities of polymersomes and new drugs, being this synergistic combination explored in this review. It also provides up-to-date examples of previous incorporations of click-compatible moieties (azide and alkyne functional groups) into polymer building blocks, enabling the "click" attachment of various functional groups and ligands, delving into the diverse range of click reactions that have been reported and employed for polymersome copolymer synthesis and the modification of polymersome surfaces, including ligand conjugation and surface modification. Overall, this review explores the current state-of-the-art of the combinatory usage, in recent years, of polymersomes with the click chemistry reaction, highlighting examples of studies of their synthesis and functionalisation strategies. [ABSTRACT FROM AUTHOR]

Nanostructured lipid carriers (NLCs) have the potential to increase the bioavailability and reduce the side effects of docetaxel (DTX). However, only a small fraction of nanoparticles given intravenously can reach a solid tumor. In situ-forming gels combined with nanoparticles facilitate local administration and promote drug retention at the tumor site. Injectable hydrogels based on poloxamer 407 are excellent candidates for this hybrid nanoparticle–hydrogel system because of their thermoresponsive behavior and biocompatibility. Therefore, this work aimed to develop injectable poloxamer hydrogels containing NLCs for intratumoral delivery of DTX. To ensure sterility, the obtained hydrogels were autoclaved (121 °C for 15 min) after preparation. Then, the incorporation of NLCs into the poloxamer hydrogels and the impact of steam sterilization on the nanocomposite hydrogels were evaluated concerning sol–gel transition, injectability, and physicochemical stability. All formulations were extruded through the tested syringe–needle systems with acceptable force (2.2–13.4 N) and work (49.5–317.7 N·mm) of injection. Following steam sterilization, injection became easier in most cases, and the physicochemical properties of all hydrogels remained practically unchanged according to the spectroscopical and thermal analysis. The rheological evaluation revealed that the nanocomposite hydrogels were liquid at 25 °C and underwent rapid gelation at 37 °C. However, their sterilized counterparts gelled at 1–2 °C above body temperature, suggesting that the autoclaving conditions employed had rendered these nanocomposite hydrogels unsuitable for local drug delivery. [ABSTRACT FROM AUTHOR]

The specific interaction between cell surface receptors and corresponding antibodies has driven opportunities for developing targeted cancer therapies using nanoparticle systems. It is challenging to design and develop such targeted nanomedicines using antibody ligands, as the final nanoconjugate's specificity hinges on the cohesive functioning of its components. The multicomponent nature of antibody-conjugated nanoparticles also complicates the characterization process. Regardless of the type of nanoparticle, it is essential to perform physicochemical characterization to establish a solid foundation of knowledge and develop suitable preclinical studies. A meaningful physicochemical evaluation of antibody-conjugated nanoparticles should include determining the quantity and orientation of the antibodies, confirming the antibodies' integrity following attachment, and assessing the immunoreactivity of the obtained nanoconjugates. In this review, the authors describe the various techniques (electrophoresis, spectroscopy, colorimetric assays, immunoassays, etc.) used to analyze the physicochemical properties of nanoparticles functionalized with antibodies and discuss the main results. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a primary malignant tumor of the central nervous system responsible for the most deaths among patients with primary brain tumors. Current therapies for GBM are not effective, with the average survival of GBM patients after diagnosis being limited to a few months. Chemotherapy is difficult in this case due to the heterogeneity of GBM and the high efficacy of the blood–brain barrier, which makes drug absorption into the brain extremely difficult. In a previous study, 3′,4′,3,4,5-trimethoxychalcone (MB) showed antiproliferative and anti-invasion activities toward GBM cells. Polymersomes (PMs) are an attractive, new type of nanoparticle for drug administration, due to their high stability, enhanced circulation time, biodegradability, and sustained drug release. In the present study, different MB formulations, PEG2000-PCL and PEG5000-PCL, were synthesized, characterized, and compared in terms of 14-day stability and in vitro cytotoxicity (hCMEC/D3 and U-373 MG). [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common and deadly primary malignant brain tumor. Current therapies are insufficient, and survival for individuals diagnosed with GBM is limited to a few months. New GBM treatments are urgent. Polymeric nanoparticles (PNs) can increase the circulation time of a drug in the brain capillaries. Polymersomes (PMs) are PNs that have been described as having attractive characteristics, mainly due to their stability, prolonged circulation period, biodegradability, their ability to sustain the release of drugs, and the possibility of surface functionalization. In this work, a poly(ethylene glycol)-ε-caprolactone (PEG-PCL) copolymer was synthesized and PMs were prepared and loaded with an hydrolytic instable compound, previously synthesized by our research team, the 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (XGAc), with promising cytotoxicity on glioblastoma cells (U-373 MG) but also on healthy cerebral endothelial cells (hCMEC/D3). The prepared PMs were spherical particles with uniform morphology and similar sizes (mean diameter of 200 nm) and were stable in aqueous suspension. The encapsulation of XGAc in PMs (80% encapsulation efficacy) protected the healthy endothelial cells from the cytotoxic effects of this compound, while maintaining cytotoxicity for the glioblastoma cell line U-373 MG. Our studies also showed that the prepared PMs can efficiently release XGAc at intratumoral pHs. [ABSTRACT FROM AUTHOR]

Actinidia arguta leaves have gained notoriety over the past years due to their rich bioactive composition with human pro-healthy effects, particularly in relation to antioxidants. Nevertheless, antioxidants are well known for their chemical instability, making it necessary to develop suitable delivery systems, such as microparticles, to provide protection and ensure a controlled release. The aim of this work was to produce polymeric particles of A. arguta leaves extract by spray-drying that may improve the oral mucositis condition. Microparticles were characterized by size, shape, antioxidant/antiradical activities, swelling capacity, moisture content, and effect on oral cells (TR146 and HSC-3) viability, with the aim to assess their potential application in this oral condition. The results attested the microparticles' spherical morphology and production yields of 41.43% and 36.40%, respectively, for empty and A. arguta leaves extract microparticles. The A. arguta leaves extract microparticles obtained the highest phenolic content (19.29 mg GAE/g) and antioxidant/antiradical activities (FRAP = 81.72 µmol FSE/g; DPPH = 4.90 mg TE/g), being perceived as an increase in moisture content and swelling capacity. No differences were observed between empty and loaded microparticles through FTIR analysis. Furthermore, the exposure to HSC-3 and TR146 did not lead to a viability decrease, attesting their safety for oral administration. Overall, these results highlight the significant potential of A. arguta leaves extract microparticles for applications in the pharmaceutical and nutraceutical industries. [ABSTRACT FROM AUTHOR]

Nanotechnology takes the lead in providing new therapeutic options for cancer patients. In the last decades, lipid-based nanoparticles—solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, and lipid–polymer hybrid nanoparticles—have received particular interest in anticancer drug delivery to solid tumors. To improve selectivity for target cells and, thus, therapeutic efficacy, lipid nanoparticles have been functionalized with antibodies that bind to receptors overexpressed in angiogenic endothelial cells or cancer cells. Most papers dealing with the preclinical results of antibody-conjugated nanoparticles claim low systemic toxicity and effective tumor inhibition, which have not been successfully translated into clinical use yet. This review aims to summarize the current "state-of-the-art" in anticancer drug delivery using antibody-functionalized lipid-based nanoparticles. It includes an update on promising candidates that entered clinical trials and some explanations for low translation success. [ABSTRACT FROM AUTHOR]

Oral mucositis (OM), a common side effect of oncological treatment, is an oral mucosal disorder characterized by painful ulcerations and increased risk of infection. The use of natural antioxidants to suppress the redox imbalance responsible for the OM condition has emerged as an interesting approach to prevent/treat OM. This study aims to explore the chestnut (Castana sativa) shells as potential active ingredient against OM. Therefore, chestnut shells were extracted at different temperatures (110–180 °C) by Subcritical Water Extraction (SWE), aiming to recover antioxidants. The extracts were also evaluated against microorganisms present in the oral cavity as well as on human oral cell lines (TR146 and HSC3). The highest phenolic content was obtained with the extraction temperature of 110 °C, exhibiting the best antioxidant/antiradical activities and scavenging efficiencies against HOCl (IC50 = 4.47 μg/mL) and ROO• (0.73 μmol TE/mg DW). High concentrations of phenolic acids (e.g., gallic and protocatechuic acids) and flavanoids (catechin, epicatechin and rutin) characterized the phenolic profile. The antimicrobial activity against several oral microorganisms present in the oral cavity during OM, such as Streptococcus, Staphylococcus, Enterococcus, and Escherichia, was demonstrated. Finally, the effects on HSC3 and TR146 cell lines revealed that the extract prepared at 110 °C had the lowest IC50 (1325.03 and 468.15 µg/mL, respectively). This study highlights the potential effects of chestnut shells on OM. [ABSTRACT FROM AUTHOR]

Actinidia arguta (Siebold & Zucc.) Planch. ex Miq. (kiwiberry) leaves are a source of phenolic compounds with pro-health biological effects, such as antioxidant and anti-inflammatory activities. Despite the huge number of studies reporting the composition of A. arguta leaves, no in vitro or in vivo studies explore its potential use as nutraceutical ingredient based on these activities. Therefore, this study aims to characterize the safety profile of kiwiberry leaf extracts using in vitro and in vivo approaches through the assessment of intestinal cell viability (Caco-2 and HT29-MTX), 3D intestinal permeation, and, most important, the redox markers, biochemical profile and liver and kidney function effects after the animal assays. Briefly, wistar rats were orally treated for 7 days with kiwiberry leaf extracts (50 and 75 mg/kg bw), water (negative control), or vitamin C (positive control). The cell viability was above 90% at 1000 μg/mL for both cells. Coumaroyl quinic acid and rutin achieved a permeation higher than 25% in the 3D intestinal model. The animal studies confirmed the extracts' ability to increase superoxide dismutase, glutathione peroxidase, and catalase content in animals' livers and kidneys while simultaneously decreasing the triglycerides content. This study highlighted the antioxidant capacity of kiwiberry leaf extracts, ensuring their efficacy and safety as a nutraceutical ingredient. [ABSTRACT FROM AUTHOR]

In the last years, the demand for new eco-friendly ingredients has increased on the cosmetic market. Consumers are more aware of sustainable principles and, simultaneously, more conscious regarding the skin aging process. Chestnut (Castanea sativa) shells are a food by-product produced in high quantities in Europe. This waste has been described as a rich source of phenolic compounds with skin biological effects, such as antioxidant, antiradical, and anti-inflammatory activities. Despite the huge number of assays reporting the richness of chestnut shell extracts in bioactive compounds as well as the development of cosmetic formulations containing these extracts, no in vivo assays have assessed their clinical efficacy in human volunteers. The aim of this study was to evaluate the effect on skin face parameters of a formulation containing a chestnut shell extract in human volunteers (n = 22) who applied the product twice per day, for 56 days. For that, biophysical techniques, including Corneometer®, Cutometer®, and PrimosPremium, were employed, allowing the quantification of skin hydration and firmness, as well as of wrinkles' depth and volume and wrinkles' skin roughness. The results demonstrated that the formulation led to a slight decrease in roughness and wrinkles' depth, although no significant differences with respect to a placebo were observed. In addition, a clear improvement of skin hydration was achieved (t0 = 54.00 Arbitrary Units (A.U.) and t56 = 58.62 A.U.). In contrast to the placebo, the active formulation increased skin firmness up to 31.76% in 50.00% of the volunteers, but without significant differences with respect to the placebo, probably due to the short period of treatment. A long-term use of the product is recommended to possibly observe significant differences in all parameters. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the optimal ultrasound-assisted extraction (UAE) conditions of antioxidants polyphenols from Actinidia arguta (Siebold & Zucc.) Planch. Ex Miq. (kiwiberry) leaves using a response surface methodology (RSM). The effects of solid:liquid ratio (2.5–10.0% w/v), time (20–60 min), and intensity (30–70 W/m2) on the total phenolic content (TPC) and antioxidant/antiradical activities were investigated. The optimal UAE conditions were achieved using a solid:liquid ratio of 10% (w/v) and an ultrasonic intensity of 30 W/m2 for 31.11 min. The results demonstrated that the optimal extract showed a high TPC (97.50 mg of gallic acid equivalents (GAE)/g dw) and antioxidant/antiradical activity (IC50 = 249.46 µg/mL for ABTS assay; IC50 = 547.34 µg/mL for DPPH assay; 1440.13 µmol of ferrous sulfate equivalents (FSE)/g dw for ferric reducing antioxidant power (FRAP)) as well as a good capacity to scavenge superoxide and hypochlorous acid (respectively, IC50 = 220.13 μg/mL and IC50 =10.26 μg/mL), which may be related with the 28 phenolic compounds quantified. The in vitro cell assay demonstrated that the optimal extract did not decrease the keratinocytes' (HaCaT) viability, while the fibroblasts' (HFF-1) viability was greater than 70.63% (1000 µg/mL). This study emphasizes the great potential of kiwiberry leaves extracted by UAE for skin application. [ABSTRACT FROM AUTHOR]

Hybrid Bayesian Networks (HBNs), which contain both discrete and continuous variables, arise naturally in many application areas (e.g., image understanding, data fusion, medical diagnosis, fraud detection). This paper concerns inference in an important subclass of HBNs, the conditional Gaussian (CG) networks, in which all continuous random variables have Gaussian distributions and all children of continuous random variables must be continuous. Inference in CG networks can be NP-hard even for special-case structures, such as poly-trees, where inference in discrete Bayesian networks can be performed in polynomial time. Therefore, approximate inference is required. In approximate inference, it is often necessary to trade off accuracy against solution time. This paper presents an extension to the Hybrid Message Passing inference algorithm for general CG networks and an algorithm for optimizing its accuracy given a bound on computation time. The extended algorithm uses Gaussian mixture reduction to prevent an exponential increase in the number of Gaussian mixture components. The trade-off algorithm performs pre-processing to find optimal run-time settings for the extended algorithm. Experimental results for four CG networks compare performance of the extended algorithm with existing algorithms and show the optimal settings for these CG networks. [ABSTRACT FROM AUTHOR]

Recent electronics advances for air transport have increased aircraft density, volume, and frequency in the airspace. These advances come with control requirements for precise navigation, coordinated Air Traffic Management (ATM) or Unmanned aircraft system Traffic Management (UTM), and proactive security. The tight tolerances of aircraft control necessitate management of spatial uncertainty, timeliness precision, and confidence assessment, which have, respectively, variance, reliability, and veracity situation awareness and assessment metrics. Meeting such airspace requirements involves the ability to evaluate how those metrics impact ATM/UTM operations, making the complex interrelationships between them a key aspect for coping with the fast worldwide growth of air transport. To support such growth, ontologies have been proposed as a promising technology for making such interrelationships explicit, while facilitating communication between avionics devices. This paper investigates the use of ontologies in support of electronic ATM/UTM operations, highlighting the use of Uncertainty Representation and the Reasoning Evaluation Framework (URREF) in realizing the ability for Air Traffic Controllers (ATCs) to semantically communicate with aircraft operators concerning physical airspace coordination. Using Avionics Analytics Ontology (AAO) endowed with the URREF, application examples based on two airspace situations are presented. Example results for northeast coast of Brazil atmospheric volcanic ash as well as for the Eyjafjallajokull volcano eruption show a 65–80% success in providing warnings to ATCs for airspace control. The paper demonstrates that an ontology-based UTM enhances the capability and accuracy of an ATM to suggest rerouting in the presence of remarkably deteriorated weather conditions. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a very poor prognosis. Its treatment is hindered by a lack of new therapeutic alternatives and the existence of the blood–brain barrier (BBB), which restricts the access of drugs commonly used in ALS, such as riluzole, to the brain. To overcome these limitations and increase brain targeting, riluzole-loaded nanostructured lipid carriers (NLC) were prepared and functionalized with lactoferrin (Lf), facilitating transport across the BBB by interacting with Lf receptors expressed in the brain endothelium. NLC were characterized with respect to their physicochemical properties (size, zeta potential, polydispersity index) as well as their stability, encapsulation efficiency, morphology, in vitro release profile, and biocompatibility. Moreover, crystallinity and melting behavior were assessed by DSC and PXRD. Nanoparticles exhibited initial mean diameters between 180 and 220 nm and a polydispersity index below 0.3, indicating a narrow size distribution. NLC remained stable over at least 3 months. Riluzole encapsulation efficiency was very high, around 94–98%. FTIR and protein quantification studies confirmed the conjugation of Lf on the surface of the nanocarriers, with TEM images showing that the functionalized NLC presented a smooth surface and uniform spherical shape. An MTT assay revealed that the nanocarriers developed in this study did not cause a substantial reduction in the viability of NSC-34 and hCMEC/D3 cells at a riluzole concentration up to 10 μM, being therefore biocompatible. The results suggest that Lf-functionalized NLC are a suitable and promising delivery system to target riluzole to the brain. [ABSTRACT FROM AUTHOR]

Quantitative structure-activity relationship (QSAR) and Quantitative structure-property relationship (QSPR) are mathematical models for the prediction of the chemical, physical or biological properties of chemical compounds. Usually, they are based on structural (grounded on fragment contribution) or calculated (centered on QSAR three-dimensional (QSAR-3D) or chemical descriptors) parameters. Hereby, we describe a Graph Theory approach for generating and mining molecular fragments to be used in QSAR or QSPR modeling based exclusively on fragment contributions. Merging of Molecular Graph Theory, Simplified Molecular Input Line Entry Specification (SMILES) notation, and the connection table data allows a precise way to differentiate and count the molecular fragments. Machine learning strategies generated models with outstanding root mean square error (RMSE) and R2 values. We also present the software Charming QSAR & QSPR, written in Python, for the property prediction of chemical compounds while using this approach. [ABSTRACT FROM AUTHOR]

The majority of works about vine-canes are focused on the evaluation of their chemical composition and antioxidant potential. To the best of our knowledge, the possible applications of produced extracts in cosmetic formulations have never been explored. The aim of the present study was to evaluate the antioxidant properties of vine-canes subcritical water extracts for use as active ingredients in the cosmetic industry. For that, the phenolic content and antioxidant activity of six vine-cane varieties, namely Alvarinho and Loureiro from the Minho region and Touriga Nacional and Tinta Roriz (TR) from both the Douro and Dão regions, were evaluated through spectrophotometric and chromatographic methods. All extracts presented similar antioxidant activity and the highest phenolic content was reported for TR variety from the Douro region (33.7 ± 1.9 mg GAE/g dw). The capacity of vine-cane extracts to capture reactive oxygen species superoxide (O2∙−) was also studied, with the highest IC50 value being obtained for Loureiro variety (56.68 ± 2.60 µg/mL). Furthermore, no adverse effects on HaCaT and HFF-1 dermal cell lines in concentrations below 100 and 1000 μg/mL, respectively, were determined. Finally, Loureiro vine-cane extract was incorporated into a topical formulation, and physical and microbiological properties were within expected values, demonstrating that vine-canes extracts can be successfully incorporated in cosmetic products. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases (NDs) bear a lot of weight in public health. By studying the properties of the blood-brain barrier (BBB) and its fundamental interactions with the central nervous system (CNS), it is possible to improve the understanding of the pathological mechanisms behind these disorders and create new and better strategies to improve bioavailability and therapeutic efficiency, such as nanocarriers. Microfluidics is an intersectional field with many applications. Microfluidic systems can be an invaluable tool to accurately simulate the BBB microenvironment, as well as develop, in a reproducible manner, drug delivery systems with well-defined physicochemical characteristics. This review provides an overview of the most recent advances on microfluidic devices for CNS-targeted studies. Firstly, the importance of the BBB will be addressed, and different experimental BBB models will be briefly discussed. Subsequently, microfluidic-integrated BBB models (BBB/brain-on-a-chip) are introduced and the state of the art reviewed, with special emphasis on their use to study NDs. Additionally, the microfluidic preparation of nanocarriers and other compounds for CNS delivery has been covered. The last section focuses on current challenges and future perspectives of microfluidic experimentation. [ABSTRACT FROM AUTHOR]

Following our previous work on the antitumor activity of acetylated flavonosides, a new acetylated xanthonoside, 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (2), was synthesized and discovered as a potent inhibitor of tumor cell growth. The synthesis involved the glycosylation of 3,6-di-hydroxyxanthone (1) with acetobromo-α-d-glucose. Glycosylation with silver carbonate decreased the amount of glucose donor needed, comparative to the biphasic glycosylation. Xanthone 2 showed a potent anti-growth activity, with GI50 < 1 μM, in human cell lines of breast, lung, and glioblastoma cancers. Current treatment for invasive brain glioma is still inadequate and new agents against glioblastoma with high brain permeability are urgently needed. To overcome these issues, xanthone 2 was encapsulated in a liposome. To increase the well-known low stability of these drug carriers, a proliposome formulation was developed using the spray drying method. Both formulations were characterized and compared regarding three months stability and in vitro anti-growth activity. While the proliposome formulation showed significantly higher stability, it was at the expense of losing its biocompatibility as a drug carrier in higher concentrations. More importantly, the new xanthone 2 was still able to inhibit the growth of glioblastoma cells after liposome formulation. [ABSTRACT FROM AUTHOR]