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Nasal drug delivery has many beneficial properties, such as avoiding the first pass metabolism and rapid onset of action. However, the limited residence time on the mucosa and limited absorption of certain molecules make the use of various excipients necessary to achieve high bioavailability. The application of mucoadhesive polymers can increase the contact time with the nasal mucosa, and permeation enhancers can enhance the absorption of the drug. We aimed to produce nanoparticles containing meloxicam potassium (MEL-P) by spray drying intended for nasal application. Various cyclodextrins (hydroxypropyl-β-cyclodextrin, α-cyclodextrin) and biocompatible polymers (hyaluronic acid, poly(vinylalcohol)) were used as excipients to increase the permeation of the drug and to prepare mucoadhesive products. Physico-chemical, in vitro and ex vivo biopharmaceutical characterization of the formulations were performed. As a result of spray drying, mucoadhesive nanospheres (average particle size 2) and ex vivo (1.47 μg/mm2) as well. After further optimization, the resulting formulations may be promising for eliciting a rapid analgesic effect through the nasal route.

Hydrogen storage in magnesium-based composites has been an outstanding research area including a remarkable improvement of the H-sorption properties of this system in the last 5 years. Numerous additives of various morphologies have been applied with great success to accelerate the absorption/desorption reactions. Different combinations of catalysts and preparation conditions have also been explored to synthesize better hydrogen storing materials. At the same time, ball milling is still commonly and effectively applied for the fabrication of Mg-based alloys and composites in order to reduce the grain size to nanometric dimensions and to disperse the catalyst particles over the surface of the host material. In this review, we present the very recent progress, from 2016 to 2021, on catalyzing the hydrogen sorption of Mg-based materials by ball milling. The various catalyzing routes enhancing the hydrogenation performance, including in situ formation of catalysts and synergistic improvement achieved by using multiple additives, will also be summarized. At the end of this work, some thoughts on the prospects for future research will be highlighted.

Nowadays, the intranasal route has become a reliable alternative route for drug administration to the systemic circulation or central nervous system. However, there are no official in vitro diffusion and dissolution tests especially for the investigation of nasal formulations. Our main goal was to study and compare a well-known and a lesser-known in vitro permeability investigation method, in order to ascertain which was suitable for the determination of drug permeability through the nasal mucosa from different formulations. The vertical diffusion cell (Franz cell) was compared with the horizontal diffusion model (Side-Bi-Side). Raw and nanonized meloxicam containing nasal dosage forms (spray, gel and powder) were tested and compared. It was found that the Side-Bi-Side cell was suitable for the investigation of spray and powder forms. In contrast, the gel was not measurable on the Side-Bi-Side cell; due to its high viscosity, a uniform distribution of the active substance could not be ensured in the donor phase. The Franz cell, designed for the analysis of semi-solid formulations, was desirable for the investigation of nasal gels. It can be concluded that the application of a horizontal cell is recommended for liquid and solid nasal preparations, while the vertical one should be used for semi-solid formulations.

Abstract Background Individually tailored cancer treatment is essential to ensure optimal treatment and resource use. Treatments for incurable metastatic non-small cell lung cancer (NSCLC) are evolving rapidly, and decision support systems (DSS) for this patient population have been developed to balance benefits and harms for decision-making. The aim of this systematic review was to inventory DSS for stage IIIB/IV NSCLC patients. Methods A systematic literature search was performed in Pubmed, Embase and the Cochrane Library. DSS were described extensively, including their predictors, model performances (i.e., discriminative ability and calibration), levels of validation and user friendliness. Results The systematic search yielded 3531 articles. In total, 67 articles were included after additional reference tracking. The 39 identified DSS aim to predict overall survival and/or progression-free survival, but give no information about toxicity or cost-effectiveness. Various predictors were incorporated, such as performance status, serum and inflammatory markers, and patient and tumor characteristics. Some DSS were developed for the entire incurable NSCLC population, whereas others were specifically for patients with brain or spinal metastases. Few DSS had been validated externally using recent clinical data, and the discrimination and calibration were often poor. Conclusions Many DSS have been developed for incurable NSCLC patients, but DSS are still lacking that are up-to-date with a good model performance, while covering the entire treatment spectrum. Future DSS should incorporate genetic and biological markers based on state-of-the-art evidence, and compare multiple treatment options to estimate survival, toxicity and cost-effectiveness.

Péter Gieszinger, Ildikó Csóka, Edina Pallagi, Gábor Katona, Orsolya Jójárt-Laczkovich, Piroska Szabó-Révész, Rita Ambrus Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Hungary Abstract: The nasal delivery of drugs offers a great alternative route to avoid adverse events and to increase patient compliance due to its advantageous properties. Besides nasal application, topical, systemic and central effects are also available. Nasal powders (NPs) have better adhesion due to the additive polymers that may be, eg, gelling or good wettability agents; thus, their bioavailability is better compared to the liquid formulations. Using nanoparticles, innovative and more efficient products can be achieved, which may lead to the improvement of different therapies. The aim of this study was to produce NP formulations containing lamotrigine (LAM) as interactive physical mixtures and nanosized LAM-based formulations. After risk assessment of the preliminary tests, the micrometric properties (particle size and morphology) and the structural properties (differential scanning calorimetry [DSC], X-ray powder diffraction [XRPD]) were investigated; thereafter, physicochemical properties (solubility, polarity) and in vitro dissolution and diffusion profiles were also examined. These product samples showed an appropriate particle size ranging 10–25 µm, while the particle size of LAM in the products was between 120 and 230 nm and the dissolved amount of drug was >60% after 5 minutes in these cases. Keywords: nanonization, nasal powder, lamotrigine, co-milling, risk assessment

The paper analyses the behavior to creasing of some woven materials made from yarns type wool used for ready-made clothes. Factors like fibrous composition, properties of constituent fibers, wovens structure parameters, mechanical properties of warp and weft yarns and finishing treatments that influenced the recovery capacity from crease/folding were investigated experimentally through several tests which revealed their importance in the process. The creasing of woven materials made from combed yarns type wool used for ready-clothes is an undesired deformation effect with temporary or permanent character, which is caused by a composed strain of bending and compression during utilization, processing or maintenance. It is manifested by the appearance of wrinkles, folds or stripes on the surface of wovens materials, thus diminishing their qualitative appearance and also their practical value. Creasing is the result of irreversible changes created through the reciprocal sliding of structural fiber components when exposed to a bending strain. Creasing is specific to oriented structures with high crystallinity (cellulosic fibers). The sliding appears because of hydrogen bond breaking which can, however, reform easy in other positions conferring a permanent character to creasing.Functional apparel will be subjected to a wide range of end uses such that a garment will be affected by intern (fibres, yarn fineness warp/weft, fabric density, thickness, fabric count) and external factors (external environment - exposure to sunlight, wind, rain, cold weather conditions, fabric/human body interaction). These factors affect the performance and behaviour of functional.

Background/Aims: Diabetic nephropathy remains a major clinical problem. The effects of prorenin might be adverse, but the literature data are controversial. We compared the renal effects of the (pro)renin receptor ((P)RR) blockade and angiotensin converting enzyme (ACE) inhibition on the progression of diabetic nephropathy in rats. Methods: Diabetes (DM) was induced by ip. streptozotocin administration in adult male Sprague-Dawley rats, followed by eight weeks of treatment with the (P)RR blocker „handle region” decoy peptide (HRP, 0,1 mg/kg/day) or with the ACE inhibitor Quinapril (Q, 50 mg/kg/day) and grouped as follows: 1. Control (n=10); 2. DM (n=8); 3. DM+HRP (n=6); 4. DM+Q (n=10); 5. DM+Q+HRP (n=10). Renal functional parameters, histology and gene expressions were evaluated. Results: HRP reduced glomerulosclerosis and podocyte desmin expression, but did not affect proteinuria and tubular ERK(1/2) phosphorylation. Both Q and Q+HRP treatment reduced proteinuria, glomerular and tubular damage, tubular TGF-ß1 expression and ERK(1/2) phosphorylation to the same extent. Conclusion: The effects of HRP were partially beneficial on diabetic kidney lesions as HRP reduced damage but did not improve tubular damage and failed to reduce ERK(1/2) phosphorylation in rats. The combination of HRP with Quinapril had no additive effects over Quinapril monotherapy on the progression of diabetic nephropathy.

Smoking is associated with shorter leucocyte telomere length (LTL), a biomarker of increased morbidity and reduced longevity. This association is widely interpreted as evidence that smoking causes accelerated LTL attrition in adulthood, but the evidence for this is inconsistent. We analysed the association between smoking and LTL dynamics in 18 longitudinal cohorts. The dataset included data from 12 579 adults (4678 current smokers and 7901 non-smokers) over a mean follow-up interval of 8.6 years. Meta-analysis confirmed a cross-sectional difference in LTL between smokers and non-smokers, with mean LTL 84.61 bp shorter in smokers (95% CI: 22.62 to 146.61). However, LTL attrition was only 0.51 bp yr−1 faster in smokers than in non-smokers (95% CI: −2.09 to 1.08), a difference that equates to only 1.32% of the estimated age-related loss of 38.33 bp yr−1. Assuming a linear effect of smoking, 167 years of smoking would be required to generate the observed cross-sectional difference in LTL. Therefore, the difference in LTL between smokers and non-smokers is extremely unlikely to be explained by a linear, causal effect of smoking. Selective adoption, whereby individuals with short telomeres are more likely to start smoking, needs to be considered as a more plausible explanation for the observed pattern of telomere dynamics.

The development of in vitro investigation models could be important using sensitive and fast methods during formulation. Intranasal applied drugs (meloxicam, lamotrigine, and levodopa) avoid the gastrointestinal tract and can achieve higher bioavailability, therefore a penetration extent is a key property. In this study, the in vitro adaptability of a modified horizontal diffusion cell was tested by using these model active pharmaceutical ingredients (APIs). The special factors consisted of the volume of the chambers, the arrangement of the stirrers, the design of probe input for real-time analysis and decreased membrane area. Membranes were impregnated by isopropyl myristate and by using phosphate buffer to evaluate the effect of API hydrophilicity on the diffusion properties. The lipophilicity of the API was proportional to the penetration extent through isopropyl myristate-impregnated membranes compared with buffer-soaked membranes. After evaluating the arithmetic mean of standard relative deviations and the penetrated extent of APIs at 15 min, Metricel® could be suggested for levodopa and meloxicam, and Whatman™ for lamotrigine. The modified model is suitable for inline, real-time detection, at nasal conditions, using small volumes of phases, impregnated membrane, to monitor the diffusion of the drug and to determine its concentration in the acceptor and donor phases.

The aim of this study was to develop an intranasal in situ thermo-gelling meloxicam-human serum albumin (MEL-HSA) nanoparticulate formulation applying poloxamer 407 (P407), which can be administered in liquid state into the nostril, and to increase the resistance of the formulation against mucociliary clearance by sol-gel transition on the nasal mucosa, as well as to improve drug absorption. Nanoparticle characterization showed that formulations containing 12–15% w/w P407 met the requirements of intranasal administration. The Z-average (in the range of 180–304 nm), the narrow polydispersity index (PdI, from 0.193 to 0.328), the zeta potential (between −9.4 and −7.0 mV) and the hypotonic osmolality (200–278 mOsmol/L) of MEL-HSA nanoparticles predict enhanced drug absorption through the nasal mucosa. Based on the rheological, muco-adhesion, drug release and permeability studies, the 14% w/w P407 containing formulation (MEL-HSA-P14%) was considered as the optimized formulation, which allows enhanced permeability of MEL through blood–brain barrier-specific lipid fraction. Cell line studies showed no cell damage after 1-h treatment with MEL-HSA-P14% on RPMI 2650 human endothelial cells’ moreover, enhanced permeation (four-fold) of MEL from MEL-HSA-P14% was observed in comparison to pure MEL. Overall, MEL-HSA-P14% can be promising for overcoming the challenges of nasal drug delivery.

In the case of capsule-based dry powder inhalation systems (DPIs), the selection of the appropriate capsule is important. The use of gelatin, gelatin-PEG, and HPMC capsules has become widespread in marketed capsule-based DPIs. We aimed to perform a stability test according to the ICH guideline in the above-mentioned three capsule types. The results of the novel combined formulated microcomposite were more favorable than those of the carrier-free formulation for all capsule types. The use of HPMC capsules results in the greatest stability and thus the best in vitro aerodynamic results for both DPI powders after six months. This can be explained by the fact that the residual solvent content (RSC) of the capsules differs. Under the applied conditions the RSC of the HPMC capsule decreased the least and remained within the optimal range, thus becoming less fragmented, which was reflected in the RSC, structure and morphology of the particles, as well as in the in vitro aerodynamic results (there was a difference of approximately 10% in the lung deposition results). During pharmaceutical dosage form developments, emphasis should be placed in the case of DPIs on determining which capsule type will be used for specific formulations.

The absorption of non-steroidal anti-inflammatory drugs (NSAIDs) through the nasal epithelium offers an innovative opportunity in the field of pain therapy. Thanks to the bonding of chitosan to the nasal mucosa and its permeability-enhancing effect, it is an excellent choice to formulate microspheres for the increase of drug bioavailability. The aim of our work includes the preparation of spray-dried cross-linked and non-cross-linked chitosan-based drug delivery systems for intranasal application, the optimization of spray-drying process parameters (inlet air temperature, pump rate), and the composition of samples. Cross-linked products were prepared by using different amounts of sodium tripolyphosphate. On top of these, the micrometric properties, the structural characteristics, the in vitro drug release, and the in vitro permeability of the products were studied. Spray-drying resulted in micronized chitosan particles (2–4 μm) regardless of the process parameters. The meloxicam (MEL)-containing microspheres showed nearly spherical habit, while MEL was present in a molecularly dispersed state. The highest dissolved (>90%) and permeated (~45 µg/cm2) MEL amount was detected from the non-cross-linked sample. Our results indicate that spray-dried MEL-containing chitosan microparticles may be recommended for the development of a novel drug delivery system to decrease acute pain or enhance analgesia by intranasal application.

Nanofibers of the poorly water-soluble antibiotic ciprofloxacin (CIP) were fabricated in the form of an amorphous solid dispersion by using poly(vinyl pyrrolidone) as a polymer matrix, by the low-cost electrospinning method. The solubility of the nanofibers as well as their in vitro diffusion were remarkably higher than those of the CIP powder or the physical mixture of the two components. The fiber size and morphology were optimized, and it was found that the addition of the CIP to the electrospinning solution decreased the nanofiber diameter, leading to an increased specific surface area. Structural characterization confirmed the interactions between the drug and the polymer and the amorphous state of CIP inside the nanofibers. Since the solubility of CIP is pH-dependent, the in vitro solubility and dissolution studies were executed at different pH levels. The nanofiber sample with the finest morphology demonstrated a significant increase in solubility both in water and pH 7.4 buffer. Single medium and two-stage biorelevant dissolution studies were performed, and the release mechanism was described by mathematical models. Besides, in vitro diffusion from pH 6.8 to pH 7.4 notably increased when compared with the pure drug and physical mixture. Ciprofloxacin-loaded poly(vinyl pyrrolidone) (PVP) nanofibers can be considered as fast-dissolving formulations with improved physicochemical properties.

This study investigated the relationship between second language (L2) listening and a range of task and listener characteristics. More specifically, for a group of 93 nonnative English speakers, the researchers examined the extent to which linguistic complexity of the listening task input and response, and speed and explicitness of the input, were associated with task difficulty. In addition, the study explored the relationship between L2 listening and listeners' working memory and listening anxiety. The participants responded to 30 multiple-choice listening items and took an English proficiency test. They also completed two working memory tasks and a listening anxiety questionnaire. The researchers analysed listening input and responses in terms of a variety of measures, using Cohmetrix, WebVocabProfiler, Praat, and the PHRASE list, in combination with expert analysis. Task difficulty and participant ability were determined by means of Rasch analysis, and correlational analyses were run to investigate the task and listener variables' association with L2 listening. The study found that L2 listening task difficulty correlated significantly with indicators of phonological, discourse, and lexical complexity and with referential cohesion. Better L2 listening performances were delivered by less anxious listeners and, depending on L2 listening measure, by those with a higher working memory capacity.

Purpose: The purpose of this study was to create a physical education (PE) attitude scale and examine how it is associated with aerobic capacity (AC). Method: Participants (n = 961, aged 15-20 years) were randomly selected from 26 Hungarian high schools. AC was estimated from performance on the Progressive Aerobic Cardiovascular and Endurance Run test, and the attitude scale had 31 items measured on a Likert scale that ranged from 1 to 5. Principal component analysis was used to examine the structure of the questionnaire while several 2-way analyses of variance and multiple linear regression (MLR) were computed to examine trends in AC and test the association between component scores obtained from the attitude scale and AC, respectively. Results: Five components were identified: health orientation in PE (C1), avoid failure in PE (C2), success orientation in PE (C3), attitude toward physical activity (C4), and cooperation and social experience in PE (C5). There was a statistically significant main effect for sex on C3 (p < 0.05), C4 (p < 0.001), and C5 (p < 0.05) indicating that boys' scores were higher than girls. The Sex × Age interaction was also statistically significant (p < 0.05) and follow-up comparisons revealed sex differences in C5 for 15-year-old participants. Girls showed statistically significant higher values than boys in C5 at the age of 16 years. MLR results revealed that component scores were significantly associated with AC (p < 0.05). Statistically significant predictors included C1, C2, C3, and C4 for boys and C2 and C4 for girls. Conclusion: The 5-component scale seems to be suitable for measuring students' attitudes toward PE. The design of the study does not allow for direct associations between attitudes and AC but suggests that these 2 might be related.

As the most abundant element in the world, hydrogen is a promising energy carrier and has received continuously growing attention in the last couple of decades. At the very moment, hydrogen fuel is imagined as the part of a sustainable and eco-friendly energy system, the “hydrogen grand challenge”. Among the large number of storage solutions, solid-state hydrogen storage is considered to be the safest and most efficient route for on-board applications via fuel cell devices. Notwithstanding the various advantages, storing hydrogen in a lightweight and compact form still presents a barrier towards the wide-spread commercialization of hydrogen technology. In this review paper we summarize the latest findings on solid-state storage solutions of different non-equilibrium systems which have been synthesized by mechanical routes based on severe plastic deformation. Among these deformation techniques, high-pressure torsion is proved to be a proficient method due to the extremely high applied shear strain that develops in bulk nanocrystalline and amorphous materials.

Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable “nano-in-micro” dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine). We targeted the respiratory zone with the microcomposites and reached a higher drug concentration with the nanonized active ingredient. We did the following investigations: particle size analysis, morphology, density, interparticular interactions, crystallinity, in vitro dissolution, in vitro permeability, in vitro aerodynamics (Andersen cascade impactor), and in silico aerodynamics (stochastic lung model). We worked out a preparation method by combining wet milling and spray-drying. We produced spherical, 3–4 µm sized particles built up by MX nanoparticles. The increased surface area and amorphization improved the dissolution and diffusion of the MX. The formulations showed appropriate aerodynamical properties: 1.5–2.4 µm MMAD and 72–76% fine particle fraction (FPF) values. The in silico measurements proved the deposition in the deeper airways. The samples were suitable for the treatment of local lung diseases.

The discovery of multi-targeting ligands of bacterial enzymes is an important strategy to combat rapidly spreading antimicrobial resistance. Bacterial DNA gyrase and topoisomerase IV are validated targets for the development of antibiotics. They can be inhibited at their catalytic sites or at their ATP binding sites. Here we present the design of new hybrids between the catalytic inhibitor ciprofloxacin and ATP-competitive inhibitors that show low nanomolar inhibition of DNA gyrase and antibacterial activity against Gram-negative pathogens. The most potent hybrid 3a has MICs of 0.5 µg/mL against Klebsiella pneumoniae, 4 µg/mL against Enterobacter cloacae, and 2 µg/mL against Escherichia coli. In addition, inhibition of mutant E. coli strains shows that these hybrid inhibitors interact with both subunits of DNA gyrase (GyrA, GyrB), and that binding to both of these sites contributes to their antibacterial activity.

Keyhaneh Karimi, Edina Pallagi, Piroska Szabó-Révész, Ildikó Csóka, Rita Ambrus Faculty of Pharmacy, Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, Hungary Abstract: Pulmonary drug delivery of ciprofloxacin hydrochloride offers effective local antibacterial activity and convenience of easy application. Spray drying is a trustworthy technique for the production of ciprofloxacin hydrochloride microparticles. Quality by design (QbD), an up-to-date regulatory-based quality management method, was used to predict the final quality of the product. According to the QbD-based theoretical preliminary parameter ranking and priority classification, dry powder inhalation formulation tests were successfully performed in practice. When focusing on the critical parameters, the practical development was more effective and was in correlation with our previous findings. Spray drying produced spherical microparticles. The dry powder formulations prepared were examined by particle size analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, differential scanning calorimetry, and in vitro drug release and aerodynamic particle size analyses were also performed. These formulations showed an appropriate particle size ranging between 2 and 4 µm and displayed an enhanced aerosol performance with fine particle fraction up to 80%. Keywords: antibiotic, carrier-free formulation, quality by design, aerodynamic evaluation, dry powder for inhalation

In the past years the commercial products for the bioscouring treatment were usually dedicated only for 100 % cotton or only for 100% lignocelluloses fabrics. The development of hemp/cotton or flax/cotton mixtures fabrics leds to the necessity of finding of the most apropiate products that could be used for different enzymatic treatments on these types of fabrics.The usage of the commercial product SERA ZYME C-PE for bioscouring treatment in ultrasound conditions on 60 % cotton + 40 % cottonised flax was studied in this work. The optimization of the Bioscouring treatment in ultrasound on 60 % cotton + 40 % hemp materials using the same commercial product was previous published. In order to assess more accurately the influence of some process parameters of the bioscouring treatment in a mathematical modeling of the process was made and a central compound rotatable program with two independent variable: x1 - the concentration of enzyme (%) and x 2 - treatment time (minutes) was used. The independent variable considered was y 1 – the weight loss. The aim of this study was to investigate the behaviour of cottonised flax/cotton mixtures for the same conditions of bioscouring treatment used as for hemp/cotton mixtures.

In this study we aimed the influence of the number of undulations of polyacrylonitrile fibers, cotton type, on the properties of yarns with Nm50/1 fineness, made on BD 200 the rotor spinning machine. Rotor spinning of the synthetic fibers is largely influenced by some characteristics of the fibers as being: the quality and quantity of the avivage, frequency of undulations and the number of defects fiber. Tensile properties and structural characteristics aspect of the yarns carried on BD 200 rotor spinning machine are determined, at the fiber content, the structural model and the technological parameters of processing, by the result of the transfer of fibers proprieties, into the meaning fiber-yarn. The yarns structural compactness, determined by the degree of twisting and tensional properties are defining for the quality of yarns and warrants the corresponding to their destination. Structural characteristics of the yarns which are characterized by complexity and diversity of their actions were studied by determining the linear irregularity (U%) , standard deviation (CV%) and the imperfections in the form of thinning (S), thickening (G), neppines (N), relative to 1000 m yarn.

The socially parasitic Alcon blue butterfly (Phengaris alcon) starts its larval stage by feeding on the seeds of gentians, after which it completes development in the nests of suitable Myrmica ant species. The host plant and host ant species can differ at the population level within a region, and local adaptation is common, but some host switches are observed. It has been suggested that one mechanism of change is through the re-adoption of caterpillars by different ant species, either through occupation of abandoned nests or take-over of established nests by competitively superior colonies. To test this question in the lab we introduced relatively strong colonies (50 workers) of alien Myrmica species to the arenas of weaker colonies (two caterpillars with six workers), and to orphaned caterpillars (two caterpillars without ants). We used caterpillars from a xerophylic population of P. alcon, and both local hosts, M. sabuleti and M. scabrinodis, testing the possibility of host switch between these two host ant species during larval development. Most of the caterpillars were successfully readopted by alien ants, and survived well. Our results suggest higher ecological plasticity in host ant usage of this butterfly than generally thought.

Our study aimed to develop an “ex tempore” reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-neuroinflammatory effect of nose-to-brain NSAID polymeric micelles was not studied previously, therefore its investigation is promising. Critical product parameters, encapsulation efficiency (89.4%), Z-average (101.22 ± 2.8 nm) and polydispersity index (0.149 ± 0.7) and zeta potential (−25.2 ± 0.4 mV) met the requirements of the intranasal drug delivery system (nanoDDS) and the targeted profile liquid formulation was transformed into a solid preservative-free product by freeze-drying. The viscosity (32.5 ± 0.28 mPas) and hypotonic osmolality (240 mOsmol/L) of the reconstituted formulation provides proper and enhanced absorption and probably guarantees the administration of the liquid dosage form (nasal drop and spray). The developed formulation resulted in more than 20 times faster MEL dissolution rate and five-fold higher nasal permeability compared to starting MEL. The prediction of IVIVC confirmed the great potential for in vivo brain distribution of MEL. The nose-to-brain delivery of NSAIDs such as MEL by means of nanoDDS as polymeric micelles offers an innovative opportunity to treat neuroinflammation more effectively.

Clinical and experimental results with inhaled sodium bicarbonate as an adjuvant therapy in cystic fibrosis (CF) are promising due to its mucolytic and bacteriostatic properties, but its direct effect has not been studied on respiratory epithelial cells. Our aim was to establish and characterize co-culture models of human CF bronchial epithelial (CFBE) cell lines expressing a wild-type (WT) or mutant (deltaF508) CF transmembrane conductance regulator (CFTR) channel with human vascular endothelial cells and investigate the effects of bicarbonate. Vascular endothelial cells induced better barrier properties in CFBE cells as reflected by the higher resistance and lower permeability values. Activation of CFTR by cAMP decreased the electrical resistance in WT but not in mutant CFBE cell layers confirming the presence and absence of functional channels, respectively. Sodium bicarbonate (100 mM) was well-tolerated by CFBE cells: it slightly reduced the impedance of WT but not that of the mutant CFBE cells. Sodium bicarbonate significantly decreased the more-alkaline intracellular pH of the mutant CFBE cells, while the barrier properties of the models were only minimally changed. These observations indicate that sodium bicarbonate is beneficial to deltaF508-CFTR expressing CFBE cells. Thus, sodium bicarbonate may have a direct therapeutic effect on the bronchial epithelium.

Most of the marketed dry powder inhalation (DPI) products are traditional, carrier-based formulations with low drug concentrations deposited in the lung. However, due to their advantageous properties, their development has become justified. In our present work, we developed an innovative, carrier-based DPI system, which is an interactive physical blend of a surface-modified carrier and a spray-dried drug with suitable shape and size for pulmonary application. Meloxicam potassium, a nonsteroidal anti-inflammatory drug (NSAID), was used as an active ingredient due to its local anti-inflammatory effect and ability to decrease the progression of cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The results of the in vitro and in silico investigations showed high lung deposition in the case of this new formulation, confirming that the interparticle interactions were changed favorably.

Nasal drug delivery has become a popular research field in the last years. This is not surprising since the nose possesses unique anatomical and physical properties. Via the nasal mucosa local, systemic, and directly central nerve systemic (CNS) effect is achievable. Powders have favorable physicochemical properties over liquid formulations. Lamotrigine (LAM) is an antiepileptic agent with a relatively mild side effect spectrum, but only available in tablet form on market. Reducing the particle size to the nano range can affect the bioavailability of pharmaceutical products. The aim of this article was to continue the work started, compare the in vitro properties of a nanonized lamotrigine containing nasal powder (nanoLAMpowder) and its physical mixture (PM) that were prepared by dry milling. Moreover, to study their trans-epithelial absorption to reach the blood and target the brain by axonal transport. Due to the dry milling technique, the particle size of LAM, their surface and also their structure changed that led to higher in vitro dissolution and permeability rate. The results of the in vivo tests showed that the axonal transport of the drug was assumable by both intranasal formulations because the drug was present in the brain within a really short time, but the LAM from the nanoLAMpowder liberated even faster.

The aim of this study was to optimize the formulation of meloxicam (MEL)-containing human serum albumin (HSA) nanoparticles for nose-to-brain via a quality by design (QbD) approach. Liquid and dried formulations of nanoparticles containing Tween 80 and without the surfactant were investigated. Various properties, such as the Z-average, zeta potential, encapsulation efficacy (EE), conjugation of MEL and HSA, physical stability, in vitro dissolution, in vitro permeability, and in vivo plasma and brain distribution of MEL were characterized. From a stability point of view, a solid product (Mel-HSA-Tween) is recommended for further development since it met the desired critical parameters (176 ± 0.3 nm Z-average, 0.205 ± 0.01 PdI, −14.1 ± 0.7 mV zeta potential) after 6 months of storage. In vitro examination showed a significantly increased drug dissolution and permeability of MEL-containing nanoparticles, especially in the case of applying Tween 80. The in vivo studies confirmed both the trans-epithelial and axonal transport of nanoparticles, and a significantly higher cerebral concentration of MEL was detected with nose-to-brain delivery, in comparison with intravenous or per os administration. These results indicate intranasal the administration of optimized MEL-containing HSA formulations as a potentially applicable “value-added” product for the treatment of neuroinflammation.

A high-energy ball milling and subsequent high-pressure torsion method was applied to synthesize nanocrystalline magnesium samples catalyzed by TiO2 or titanate nanotubes. The microstructure of the as-milled powders and the torqued bulk disks was characterized by X-ray diffraction. The recorded diffractograms have been evaluated by the convolutional multiple whole profile fitting algorithm, which provided microstructural parameters (average crystal size, crystallite size distribution, average dislocation density). The morphology of the nanotube-containing disks has been examined by high-resolution transmission electron microscopy. The effect of the different additives and preparation conditions on the hydrogen absorption behavior was investigated in a Sieverts’-type apparatus. It was found that the ball-milling route has a prominent effect on the dispersion and morphology of the titanate nanotubes, and the absorption capability of the Mg-based composite is highly dependent on these features.

This investigation examined two techniques that may help learners focus on second language (L2) constructions when recasts are provided during meaning-based communicative activities: altering the cognitive complexity of tasks and manipulating the input frequency distributions of target constructions. We first independently assessed the validity of our cognitive task complexity manipulation by means of expert judgments, dual-task methodology, and eye tracking. Next, in our main study, we employed a pretest-posttest design with two treatment sessions. The participants were 51 adult English L2 learners, randomly assigned to one of four experimental groups or a control group. All experimental groups received recasts but differed as to whether they carried out simple tasks with lower reasoning demands or complex tasks with higher reasoning demands, and whether they received skewed or balanced input of the linguistic target, the past counterfactual construction. An oral production test and two written receptive tests were utilized to measure changes in participants' knowledge. Our results revealed no effects for the input frequency manipulations, but participants achieved higher oral production gains under the simple task condition.

This work has shown to you a study about the determination of tensile strenght by three methods of stress, using the four varieties of the cotton fibers: Russian 2A, Russian 1A, Sudanese Baracat 5x5, Pakistani SLM (Medium IV). The methods of the tensile stress used in this study are: the method of requesting of a bundle containing all categories of fibers from the sample, using the DS-3M dynamometer; the the method of application of flat bundles of fibers containing fibers previously sorted by length classes using the mechanical fibrometer and then subjected to tensile strength determination on the dynamometer DS-3M; the method of application of the three fiber bundles corresponding to the class with the highest fiber content. From the comparative analysis of these three methods of stress,we can find that the index for assessing the tensile strength, called the toughness mode, obtained by the third method, combining the advantages of the first method and eliminating the disadvantages of the second, can be an optimal index to express it. From the experimental results and the graphical representations as the distribution diagram of the cotton fiber length, depending on their mass,we can find that the fiber mass belonged to the classes with the highest fiber content is about 35-55% of the total mass of the sample, an enough approximation for the tenacity, the toughness mode, to be expressed, using a coefficient ,named the average tenacity, measured by the disclosed methods . The third proposed method has a double productivity of conventional methods, it reduces the time required for all determinations by 55%, it is not required the counting of the fibers per a milligram and also, it is possible to determine the mode length of the fibers at the same time /with the tenacity.