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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]

Sixteen geosterane derivatives were synthesized in up to 57 % overall yields in four steps harnessing the olefin cross‐metathesis (OCM) and Metal hydride H atom transfer (MHAT) or homogeneous hydrogenation reactions as key steps. Drawing on this strategy, the diastereomeric ratio (d. r.) reached up to 24 : 1 for the thermodynamic isomer and 7 : 1 for the other isomer in the hydrogenation step. In a geological sample from northeast Brazil, we confirmed the putative structures previously assumed as methyl 2‐(3α‐5αH‐cholestan) acetate, methyl 2‐(3β‐5αH‐cholestan)acetate, and methyl 6‐(3β‐5αH‐cholestan)hexanoate, as well three new molecular fossils of approximately 120 million years old. We also proved the migration marking ability of those carboxylic acids derived from forerunner geosteranes during an oil migration event, which suggests their aptitudes as molecular odometers. Our approach demonstrated swiftness and effectiveness in preparing a molecular library of geological biomarkers would also be appropriate to generate stereochemical diversity in molecular libraries for medicinal chemistry and natural product anticipation. [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]

[Display omitted] • Natural products offer alternatives for disease prevention and treatment; • Kiwiberry has diverse bioactive compounds & biological activities; • Kiwiberry's bioactive compounds show promise in glioblastoma treatment & prevention; • Review explores kiwiberry's glioblastoma effects, offering therapy insights. In recent years, there has been a significant demand for natural products as a mean of disease prevention or as an alternative to conventional medications. The driving force for this change is the growing recognition of the abundant presence of valuable bioactive compounds in natural products. On recent years Actinia arguta fruit, also known as kiwiberry, has attracted a lot of attention from scientific community due to its richness in bioactive compounds, including phenolic compounds, organic acids, vitamins, carotenoids and fiber. These bioactive compounds contribute to the fruit's diverse outstanding biological activities such as antioxidant, anti-inflammatory, neuroprotective, immunomodulatory, and anti-cancer properties. Due to these properties, the fruit may have the potential to be used in the treatment/prevention of various types of cancer, including glioblastoma. Glioblastoma is the most aggressive form of brain cancer, displaying 90 % of recurrence rate within a span of 2 years. Despite the employment of an aggressive approach, the prognosis remains unfavorable, emphasizing the urgent requirement for the development of new effective treatments. The preclinical evidence suggests that kiwiberry has potential impact on glioblastoma by reducing the cancer self-renewal, modulating the signaling pathways involved in the regulation of the cell phenotype and metabolism, and influencing the consolidation of the tumor microenvironment. Even though, challenges such as the imprecise composition and concentration of bioactive compounds, and its low bioavailability after oral administration may be drawbacks to the development of kiwiberry-based treatments, being urgent to ensure the safety and efficacy of kiwiberry for the prevention and treatment of glioblastoma. This review aims to highlight the potential impact of A. arguta bioactive compounds on glioblastoma, providing novel insights into their applicability as complementary or alternative therapies. [ABSTRACT FROM AUTHOR]

Actinidia arguta is a climbing, fruit plant that recently generated a spread interest in many regions of the world, due to world globalization and knowledge expansion. During its production, different by-products are generated, such as fruits, leaves, stems, flowers and roots, being characterized by a rich bioactive composition that wise the scientific community for its health effects. Inboard of this panoply of valuable bioactive compounds, vitamin C, chlorogenic and neochlorogenic acids, caffeic acid, quercetin, catechin, kaempferol, p -coumaric acid, minerals and fatty acids play critical roles. As a result, the valorization and reuse of these by-products is a challenge, particularly for producers. This review aims to summarize the potential cosmetic and medical skincare applications of the different bioactive compounds from A. arguta by-products, describing and exploring their potential to contribute as active ingredients based on the biological activities reported. Simultaneously, a critical analysis of the patents available on the market regarding its use as cosmetic and medical skincare ingredient is provided. Cosmetic and medical skincare products could be a sustainable and green option for the use of A. arguta by-products bioactive compounds. Apart from contribute to skin appearance and health, the addition of these active compounds to the final cosmetic and pharmaceutical products may also provide skin beneficial effects such as photoprotection, anti-aging and anti-inflammatory effects, also acting as depigmenting and emollients, among other activities. Besides that, the impact on food by-product valorization and circular economy will be enormous. [Display omitted] • Actinia arguta by-products are rich in bioactive compounds with skin effects. •The use of A. arguta by-products in topical formulations is extremely promising. •Skin health benefits are enormous. •Few patents are available on the market with A. arguta as skin ingredient. •Add value to fruit byproducts. [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]

• Dissolvable pullulan microneedles were successfully prepared by solvent casting. • Pullulan-insulin microneedles successfully penetrate through the skin. • Storage at 4, 20 and 40 °C maintained the secondary structure of insulin. • Pullulan microneedles deliver 87% of insulin, 120 min after insertion. • Pullulan-insulin microneedles are non-cytotoxic towards human keratinocyte cells. The present study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin, envisioning the non-invasive treatment of diabetes. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (T dmax = 294 °C) and mechanical properties (>0.15 N needle−1), penetrating skin up to 381 μm depth, as revealed by in vitro skin tests. After application into human abdominal skin in vitro , the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. These findings suggest that PL MNs have potential to deliver insulin transdermally, thus avoiding its subcutaneous administration. [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]

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]

[Display omitted] • Pistacia vera L. shell extract was optimized by a response surface methodology approach. • The HPLC/ESI-MS/MS allowed to identify the main constituents of the optimized extract. • The optimized extract exhibited a significant antioxidant/antiradical activity. • The optimized extract exhibited a notable α-amylase and α-glucosidase inhibitory activity. • Intestinal cell viability (Caco-2, HT29-MTX) was not affected by the optimized extract. Pistacia vera shells, an abundant agricultural by-product, are a rich source of undiscovered bioactive compounds. This study employed a response surface methodology (RSM) approach to optimize the microwave-assisted extraction of antioxidants. The highest total phenolic content, and antioxidant activity were achieved under the optimized extraction conditions (20 % ethanol, 1000 W, 135 s, and solvent-to-solid ratio of 27 mL/g). The resulting extract (OPVS-E) included gallic acid derivatives, hydrolysable tannins, flavonoids, fatty acids, and anacardic acids. Remarkably, OPVS-E displayed potent inhibitory activity against α-amylase (IC 50 = 2.05 μg/mL) and α-glucosidase (IC 50 = 41.07 μg/mL), by far more powerful than the anti-diabetic drug acarbose, OPVS-E exhibited a strong antiradical capacity against reactive oxygen species (ROS) without causing toxicity in intestinal cells (HT29-MTX and Caco-2). These findings introduce OPVS-E as a potential novel dual-action nutraceutical ingredient, able to mitigate postprandial hyperglycemia and counteract the ROS overproduction occurring in type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Abstract: The original smectite clay mineral has been collected from Amazon region, Brazil. The compound 2-aminomethylpyridine (AMP) was anchored onto Amazon smectite surface by heterogeneous route. The natural (SMC) and modified (SMCAMP) smectite samples were characterized by elemental analysis, scanning electron microscopy, N2 adsorption, X-ray diffraction, and silicon-29 and carbon-13 nuclear magnetic resonance. Due to the increment of basic centers attached to the pendant chains, the metal adsorption capability of the final chelating material, was found to be higher than the precursor. The ability of these materials to remove Cr(VI) from aqueous solution was followed by a series of adsorption isotherms at room temperature and pH 4.0. The maximum number of moles adsorbed was determined to be 1.16 and 1.87mmolg−1 for SMC and SMCAMP, respectively. In order to evaluate the clay samples as adsorbents in dynamic system, a glass column was fulfilled with clay samples (1.0g) and it was fed with 2.0×10−4 moldm−3 Cr(VI) at pH 4.0. The energetic effects caused by metal cation adsorption were determined through calorimetric titrations. Thermodynamics indicated the existence of favorable conditions for such Cr(VI)–nitrogen interactions. [Copyright &y& Elsevier]

Abstract: The original sepiolite clay mineral has been collected from Amazon region, Brazil. The compound 2-aminomethylpyridine (AMP) was anchored onto Amazon sepiolite surface by heterogeneous route. The natural (SPT) and modified (SPTAMP) sepiolite samples were characterized by elemental analysis, SEM, N2 adsorption, and nuclear magnetic nuclei of 29Si and 13C. The well-defined peaks obtained in the 13C NMR spectrum in the 0–160ppm region confirmed the attachment of organic functional groups as pendant chains bonded into the porous clay. The ability of these materials to remove As(V) from aqueous solution was followed by a series of adsorption isotherms at room temperature and pH 4.0. The maximum number of moles adsorbed was determined to be 7.26×10−2 and 11.70×10−2 mmolg−1 for SPT and SPTAMP, respectively. In order to evaluate the clay samples as adsorbents in dynamic system, a glass column was fulfilled with clay samples (1.0g) and it was fed with 2.0×10−2 mmoldm−3 As(V) at pH 4.0. The energetic effects caused by metal cations adsorption were determined through calorimetric titrations. Thermodynamics indicated the existence of favorable conditions for such As(V)–nitrogen interactions. [Copyright &y& Elsevier]

[Display omitted] • Amytrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. • Riluzole was loaded into lipid nanoparticles (SLN and NLC) for ALS therapy. • Optimized SLN and NLC exhibited desirable characteristics for brain delivery. • Lipid nanoparticles were stable, promoting a slow and sustained release of riluzole. • Nanoparticles showed good biocompatibility with brain microvascular endothelial cells. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, with a median survival of only 2 to 4 years. Riluzole, a drug commonly used in the management of ALS, has a low aqueous solubility and limited bioavailability. ALS treatment is also hindered by the presence of the blood–brain barrier (BBB) that preserves the delicate homeostasis of the cerebral milieu, isolating it and making brain drug delivery exceptionally hard. To overcome these issues, the use of lipid nanocarriers, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), is a promising strategy. In this study, SLN and NLC were prepared and optimized to facilitate riluzole uptake into the brain for ALS therapy. The lipid nanoparticles were characterized through different techniques, with respect to their physicochemical properties (size, zeta potential (ZP), polydispersity index (PDI)), as well as encapsulation efficiency, morphology, stability, in vitro release, crystallinity, and biocompatibility. Riluzole-loaded nanocarriers exhibited characteristics suitable for brain delivery, including mean diameters between 147.2 and 203.1 nm, low PDI (<0.3), and negative ZP between −22.5 and −27.5 mV. Additionally, they were physically stable over 3 months under storage conditions (5 ℃ and 25 ℃), promoting a slow and sustained release of the drug, which was shown to be inside the core of the lipid matrix. Cytotoxicity assays demonstrated that both SLN and NLC did not significantly affect the viability of an hCMEC/D3 cell monolayer at a riluzole concentration up to 10 μM. The results suggest that the developed nanocarriers could be a viable platform to target riluzole to the central nervous system (CNS). Nevertheless, further in vitro and in vivo studies are needed to validate their therapeutic efficacy and safety. [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]

Designing hydrogels with high-strength and stiffness remains a challenge, limiting their usage in several applications that involve load-bearing. In this work, in situ incorporation of different amounts of graphene oxide (GO) into poly(2-hydroxyethyl methacrylate) (pHEMA) was used to create hydrogels with outstanding stiffness (Young's modulus of up to 6.5 MPa, 8.3x higher than neat pHEMA) and tensile resistance (ultimate tensile strength of up to 1.14 MPa, 7.4x higher than neat pHEMA) without affecting the water absorption capacity, surface wettability and cytocompatibility of pHEMA. Such magnitude of improvement in Young's modulus and ultimate tensile strength was never before described for GO incorporation in hydrogels. Moreover, these stiffness and tensile resistance values are higher than the ones of most hydrogels (few hundred kPa), achieving a stiffness comparable to polydimethylsiloxane (PDMS), cartilage and artery walls and a tensile resistance similar to rigid foams, PDMS and cork. These new materials open a wide range of applications for pHEMA in different fields. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The utilization of natural compounds, such as phenolic acids and biopolymers, in the healthcare domain is gaining increasing attention. In this study, bacterial nanocellulose (BC) membranes were loaded with ionic liquids (ILs) based on phenolic acids. These ionic compounds, with improved solubility and bioavailability, were prepared by combining the cholinium cation with anions derived from caffeic, ellagic and gallic acids. The obtained BC-ILs membranes were homogeneous, conformable and their swelling ability agreed with the solubility of each IL. These membranes revealed a controlled ILs dissolution rate in the wet state and high antioxidant activity. In vitro assays performed with Raw 264.7 macrophages and HaCaT keratinocytes revealed that these novel BC-ILs membranes are non-cytotoxic and present relevant anti-inflammatory properties. Diffusion studies with Hanson vertical diffusion cells showed a prolonged release profile of the ILs from the BC membranes. Thus, this work, successfully demonstrates the potential of BC-ILs membranes for skin treatment. [ABSTRACT FROM AUTHOR]

The blood-brain barrier (BBB) restricts the access of therapeutic agents to the brain, complicating the treatment of neurological diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery to the central nervous system (CNS), the potential of nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, the surface of the nanocarriers can be modified with ligands that interact with the BBB, enhancing their uptake and penetration across the brain endothelium by different physiological mechanisms, such as receptor- or transporter-mediated transcytosis. This review seeks to provide an overview of active targeting in brain delivery, while highlighting the potential of functionalized lipid nanocarriers to treat brain diseases. Therefore, in the first sections, we discuss the importance of active targeting in CNS drug delivery, present the different ligands commonly used for functionalization, as well as summarize the state of the art of the most recent and relevant studies of surface-modified lipid nanosystems developed for neurological disorders. Lastly, challenges hindering clinical translation are discussed, and critical insights and future perspectives outlined. Although some limitations have been identified, it is expected that in the upcoming years these nanosystems will be an established approach. [Display omitted] • The blood-brain barrier (BBB) hinders the treatment of neurodegenerative diseases. • Lipid nanocarriers are a promising approach to improve brain drug targeting. • Functionalization of nanocarriers with ligands increases BBB selectivity uptake. • The main ligands are glycoproteins, antibodies, apolipoproteins, and peptides. • Robust regulatory and manufacturing practices are needed for clinical translation. [ABSTRACT FROM AUTHOR]

Current challenges in the development of scaffolds for bone regeneration include the engineering of materials that can withstand normal dynamic physiological mechanical stresses exerted on the bone and provide a matrix capable of supporting cell migration and tissue ingrowth. The objective of the present work was to develop and characterize a hybrid polymer–ceramic injectable system that consists of an alginate matrix crosslinked in situ in the presence of strontium (Sr), incorporating a ceramic reinforcement in the form of Sr-rich microspheres. The incorporation of Sr in the microspheres and in the vehicle relies on the growing evidence that Sr has beneficial effects in bone remodeling and in the treatment of osteopenic disorders and osteoporosis. Sr-rich porous hydroxyapatite microspheres with a uniform size and a mean diameter of 555 μm were prepared, and their compression strength and friability tested. A 3.5% ( w / v ) ultrapure sodium alginate solution was used as the vehicle and its in situ gelation was promoted by the addition of calcium (Ca) or Sr carbonate and Glucone-δ-lactone. Gelation times varied with temperature and crosslinking agent, being slower for Sr than for Ca, but adequate for injection in both cases. Injectability was evaluated using a device employed in vertebroplasty surgical procedures, coupled to a texture analyzer in compression mode. Compositions with 35% w of microspheres presented the best compromise between injectability and compression strength of the system, the force required to extrude it being lower than 100 N. Micro CT analysis revealed a homogeneous distribution of the microspheres inside the vehicle, and a mean inter-microspheres space of 220 μm. DMA results showed that elastic behavior of the hybrid is dominant over the viscous one and that the higher storage modulus was obtained for the 3.5%Alg–35%Sr-HAp-Sr formulation. [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]

Highlights: [•] BC membranes were used as transdermal systems for diclofenac sodium. [•] BC-diclofenac sodium loaded membranes were very homogeneous and quite flexible. [•] Permeation studies through human epidermis were conducted using Franz cells. [•] The results showed therapeutic feasibility when compared with commercial products. [ABSTRACT FROM AUTHOR]

Abstract: The Figueira Branca Suite (FBS) comprises a layered mafic–ultramafic complex which together with mafic–felsic plugs makes up a string of NW-trending intrusive bodies that are emplaced into the Jauru domain (Rio Negro-Juruena province; 1.80–1.60Ga). This domain comprises Orosirian calc-alkaline rocks and coeval metamorphic volcanic–sedimentary associations, intruded by voluminous granitoid plutons resulted from outboard Cachoeirinha (1587–1522Ma) and Santa Helena (1485–1420Ma) accretionary orogens that eventually created the Rondonian-San Ignacio province along the SW margin of the proto-Amazonian Craton. SHRIMP U–Pb age in zircon for one cumulatic gabbro from the FBS yielded a concordia intercept age of 1425.5±8.0Ma (MSWD=1.11). Another gabbroic plug which crops out to the East gives a similar within error concordia intercept zircon age of 1415.9±6.9Ma (MSWD=0.25), whereas a nearby monzogranite yields a concordia intercept zircon age of 1428.9±2.8Ma (MSWD=1.30). All these results are crystallization ages and constrain an important intraplate magmatic event within the Orosirian continental crust at the time of outboard Santa Helena orogen. On the other hand, igneous titanite from another gabbro located to the West of the FBS yielded a weighted mean 207Pb/206Pb crystallization age of 1541±23Ma (MSWD=0.74). Therefore this rock is not genetically associated with the FBS, as previously suggested by the field information. Additional Nd–Sr isotopic analyses of the FBS mafic–ultramafic rocks and coeval gabbro showed comparable ɛ Nd(1.42Ga) values (+3.0 to +4.7) and variable ɛ Sr(1.42Ga) ones (−39.1 to −8.1). These data plot in the depleted field quadrant of the Nd–Sr diagram, indicating a significant influence of the MORB end-member reservoir in the magma genesis. This interpretation is similarly supported by comparison of the Nd evolutionary path of the FBS with those that characterize the isotopic evolution of the Jauru crust and the Cachoeirinha and Santa Helena intrusive plutons. The bulk isotopic signature allows the genetic relationship among the Santa Helena Suite and the FBS and coeval rocks. The anorogenic character of the FBS is supported by the geologic framework of the Jauru domain, given that the emplacement took place under an extensional regime, associated with the recognized regional NW-trending structures. 40Ar–39Ar analyses were carried out in mafic rocks that are assigned to the FBS. Biotite from a gabbronorite yielded an ideogram age of 1222±5Ma while a nearby troctolite yielded plateau biotite ages of 1275±4Ma and 1268±4Ma. These ages are minimum estimates of the regional cooling of the FBS. One gabbro of the Alto Jauru Group yields a 40Ar–39Ar plateau age of 1781±15Ma, interpreted as the time of regional cooling that succeeded continental accretion and metamorphism at Orosirian times. Later on heterogenous crustal thickening and uplift took place from West to East, as response from the Cachoeirinha and Santa Helena orogen dynamics, which is marked by the 1539–1510Ma and 1452–1322Ma 40Ar–39Ar age-patterns, respectively. The available apparent ages suggest that Cachoeirinha crust was subjected to a fast exhumation rate (ca. 50m.y.), as estimated by the zircon–titanite–hornblende–biotite time-path, while the Santa Helena crust seems to display a lower exhumation rate. Particularly, the youngest 40Ar–39Ar biotite age (1322Ma) available for the Santa Helena crust signals the post-tectonic phase of the Rondonian-San Ignacio province. [Copyright &y& Elsevier]

This work compares the estimation of the particle size distribution of a pharmaceutical powder using near-infrared spectroscopy (NIRS), powder flowability properties, and components concentration. The estimations were made by considering the former data blocks separately and together using a multi-block approach. The powders were based on a formulation of paracetamol as the pharmaceutical active ingredient. The reference method used to determine particle size distribution was sieving. Partial least squares methods were used to estimate the multivariate regression models, and the results were compared in terms of figures of merit. It was shown that the partial least squares methods gave similar prediction errors. Regarding the data blocks used, the NIRS block was proven the most advantageous to estimate the particle size distribution. The prediction error of the NIRS block was similar to the other data blocks with additional advantages such as less generalization problems and the possibility of its use to predict additional physical and chemical properties with an improvement to analysis time. The multi-block approach produced the worst results but nevertheless allowed a deeper understanding of the individual contributions of the data blocks in the prediction of the particle size distribution. [ABSTRACT FROM AUTHOR]

Abstract: The physical properties of pharmaceutical powders are of upmost importance in the pharmaceutical industry. The knowledge of their flow properties is of critical significance in operations such as blending, tablet compression, capsule filling, transportation, and in scale-up operations. Powders flow properties are measured using a number of parameters such as, angle of repose, compressibility index (Carr''s index) and Hausner ratio. To estimate these properties, specific and expensive equipment with time-consuming analysis is required. Near infrared spectroscopy is a fast and low-cost analytical technique thoroughly used in the pharmaceutical industry in the quantification and qualification of products. To establish the potential of this technique to determine the parameters associated with the flow properties of pharmaceutical powders, blended powders based on paracetamol as the active pharmaceutical ingredient were constructed in pilot scale. Spectra were recorded on a Fourier-transform near infrared spectrometer in reflectance mode. The parameters studied were the angle of repose, aerated and tapped bulk density. The correlation between the reference method values and the near infrared spectrum was performed by partial least squares and optimized in terms of latent variables using cross-validation. The near infrared based properties predictions were compared with the reference methods results. Prediction errors, which varied between 2.35% for the angle of repose, 2.51% for the tapped density and 3.18% for the aerated density, show the potential of NIR spectroscopy in the determination of physical properties affecting the flowability of pharmaceutical powders. [Copyright &y& Elsevier]

Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet-mediated oxidative damage and provides a straightforward way to strengthen the endogenous protection system. However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron-chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40°. The IC50 found for the iron chelation and DPPH scavenging assays were 132.94 ± 9.72 and 12.58 ± 0.54 µg/ml (mean ± S.E.M.), respectively. The total phenolic content was found to be 283.8 ± 8.74 mg GAE/g extract (mean ± S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application. [ABSTRACT FROM AUTHOR]

The topical application of antioxidants may be beneficial for the protection of the skin against UV damage. An extract of Quercus robur leaves was prepared and evaluated considering its putative application as topical antioxidant. The solvent and extractive method selection was monitored by 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging activity and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron chelating activity and the phenolic composition (HPLC/DAD) were assessed on the extract obtained under optimized conditions. Skin irritation potential was investigated by performing an in vivo patch test in 19 volunteers. The extraction solvent which resulted in the highest activity was ethanol:water (4:6) and thus it was selected for further preparation of this extract. The IC50s for the iron chelation and DPPH scavenging assays were 153.8 ± 26.3 µg.mL-1 and 7.53 ± 0.71 µg.mL-1 (mean ± SD), respectively. The total phenolic content was found to be 346.3 ± 6.7 mg gallic acid equivalents (GAE)/g extract (mean ± SD). Three phenolic compounds were identified in the extract namely: ellagic acid, rutin and hyperoside. The major identified component was ellagic acid. The patch test carried out showed that the extract can be regarded as safe for topical application. [ABSTRACT FROM AUTHOR]

Abstract: The growing interest in the substitution of synthetic food antioxidants by natural ones has fostered research on vegetable sources and on the screening of raw materials, for identifying new antioxidants. In the present study, an ethanol:water (4:6) extract from Juglans regia leaves was evaluated for its putative in vitro scavenging effects on reactive oxygen species (ROS) [hydroxyl radical (HO ), superoxide radical , peroxyl radical (ROO ) and hydrogen peroxide (H2O2)] and reactive nitrogen species (RNS) [nitric oxide ( NO) and peroxynitrite anion (ONOO−)]. The extract presented a potent scavenging activity against all the reactive species tested, all the IC50s being found at the μg/mL level. IC50s (mean±SE) for the ROS and H2O2 were 47.6±4.6, 383±17μg/mL, respectively. The oxygen radical absorbance capacity (ORAC) value obtained for ROO was 2.17±0.22μmol Trolox equivalents/mg extract. The IC50s for NO and ONOO− were 1.95±0.29 and 1.66±0.10μg/mL, respectively. The content of total phenolics was 270±3mg of gallic acid equivalents (GAE)/g of lyophilised extract. These results showed that J. regia leaf extracts can be used as an easily accessible source of natural antioxidants. [Copyright &y& Elsevier]

Bone graft infections are serious complications in orthopaedics and the growing resistance to antibiotics is increasing the need for antibacterial strategies. The use of magnesium oxide (MgO) is an interesting alternative since it possesses broad-spectrum antibacterial activity. Additionally, magnesium ions also play a role in bone regeneration, which makes MgO more appealing than other metal oxides. Therefore, a bone substitute composed of hydroxyapatite and MgO (HAp/MgO) spherical granules was developed using different sintering heat-treatment cycles to optimize its features. Depending on the sintering temperature, HAp/MgO spherical granules exhibited distinct surface topographies, mechanical strength and degradation profiles, that influenced the in vitro antibacterial activity and cytocompatibility. A proper balance between antibacterial activity and cytocompatibility was achieved with HAp/MgO spherical granules sintered at 1100 ºC. The presence of MgO in these granules was able to significantly reduce bacterial proliferation and simultaneously provide a suitable environment for osteoblasts growth. The angiogenic and inflammation potentials were also assessed using the in vivo chicken embryo chorioallantoic membrane (CAM) model and the spherical granules containing MgO stimulated angiogenesis without increasing inflammation. The outcomes of this study evidence a dual effect of MgO for bone regenerative applications making this material a promising antibacterial bone substitute. [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]

Alterations of the physical-chemical properties of the oceans due to anthropogenic activities are, at present, one of the most concerning environmental issues studied by researchers. One of these issues is ocean acidification, mainly caused by overproduction and release of carbon dioxide (CO 2) from anthropogenic sources. Another component of environmental degradation is related to the production and release of potential toxic compounds, namely active pharmaceutical ingredients, into the aquatic environment that, combined with oceanic acidification, can cause unpredictable and never before considered deleterious effects on non-target marine organisms. Regarding this issue, the hereby study used predictions of future ocean acidification to simulate realistic scenarios of environmental exposure to a common therapeutic drug, salicylic acid (SA), in the marine gastropod Gibbula umbilicalis under different pH values. This species was exposed to a range of pH values (8.2, 7.9 and 7.6), and to already reported environmentally realistic concentrations (5, 25 and 125 μg/L) of SA. To evaluate the effects of these environmental stressors, key physiological biomarkers (GSTs, CAT, TBARS, AChE and COX) and shell hardness (SH) were quantified. Results from the present study showed that CAT and GSTs activities were enhanced by SA under water acidification; increased lipid peroxidation was also observed in organisms exposed to SA in more acidic media. In addition, the hereby study demonstrated the neurotoxic effects of SA through the inhibition of AChE. Effects were also observed in terms of COX activity, showing that SA absorption may be affected by water acidification. In terms of SH, the obtained data suggest that SA may alter the physical integrity of shells of exposed organisms. It is possible to conclude that the combination of seawater acidification and exposure to toxic xenobiotics (namely to the drug SA) may be strenuous to marine communities, making aquatic biota more susceptible to xenobiotics, and consequently endangering marine life in an unpredictable extent. • Physiological alterations were enhanced under SA exposure at lower pH levels. • Lipid peroxidation increased after seawater acidification. • Neurotoxic effects were reported under SA exposure. • Prostaglandins biosynthesis pathway inhibited by SA absorption at lower pH levels. [ABSTRACT FROM AUTHOR]

The article presents a study on dyke swarms in Sao Francisco cratons in Brazil. The petrogenetc and tectonic significance of the dyke swarms are studied.The emplacement ages and coupled geo chemical and isotopic data in the light of long lived poly cyclic evolution of the basement rocks and the underneath subcontinental mantle through time are reassessed.

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]