bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Polymer-Based Nanocarriers for Co-Delivery of Curcumin and Selected Anticancer Drugs
Authors: Alven Sibusiso , Aderibigbe Blessing Atim
Published: August 2020

Cancer remains a heavy health burden resulting in a high rate of mortality around the world. The presently used anticancer drugs suffer from several shortcomings, such as drug toxicity, poor biodegradability and bioavailability, and poor water solubility and drug resistance. Cancer is treated effectively by combination therapy whereby two or more anticancer drugs are employed. Most of the combination chemotherapies result in a synergistic effect and overcome drug resistance. Furthermore, the design of polymer-based nanocarriers for combination therapy has been reported by several researchers to result in promising therapeutic outcomes in cancer treatment. Curcumin exhibits good anticancer activity but its poor bioavailability has resulted in its incorporation into several polymer-based nanocarriers resulting in good biological outcomes. Furthermore, the incorporation of curcumin together with other anticancer drugs have been reported to result in excellent therapeutic outcomes in vivo and in vitro. Due to the potential of polymer-based nanocarriers, this review article will be focused on the design of polymer-based nanocarriers loaded with curcumin together with other anticancer drugs.
Tuning of Ag Nanoparticle Properties in Cellulose Nanocrystals/Ag Nanoparticle Hybrid Suspensions by H2O2 Redox Post-Treatment: The Role of the H2O2/AgNP Ratio
Authors: Musino Dafne , Rivard Camille , Novales Bruno , Landrot Gautier , Capron Isabelle
Published: August 2020

Hybrid nanoparticles involving 10-nm silver nanoparticles (AgNPs) nucleated on unmodified rod-like cellulose nanocrystals (CNCs) were prepared by chemical reduction. H2O2 used as a post-treatment induced a size-shape transition following a redox mechanism, passing from 10-nm spherical AgNPs to 300-nm triangular or prismatic NPs (AgNPrisms), where CNCs are the only stabilizers for AgNPs and AgNPrisms. We investigated the role of the H2O2/AgNP mass ratio (α) on AgNPs. At α values above 0.20, the large amount of H2O2 led to extensive oxidation that produced numerous nucleation points for AgNPrisms on CNCs. On the contrary, for α below 0.20, primary AgNPs are only partially oxidized, releasing a reduced amount of Ag+ ions and thus preventing the formation of AgNPrisms and reforming spherical AgNPs. While XRD and EXAFS reveal that the AgNP fcc crystal structure is unaffected by the H2O2 treatment, the XANES spectra proved that the AgNP–AgNPrism transition is always associated with an increase in the metallic Ag fraction (Ag0). In contrast, the formation of new 15-nm spherical AgNPs keeps the initial Ag0/Ag+ ratio unmodified. For the first time, we introduce a complete guide map for the fully-controlled preparation of aqueous dispersed AgNPs using CNC as a template.
Facile Synthesis of “Boron-Doped” Carbon Dots and Their Application in Visible-Light-Driven Photocatalytic Degradation of Organic Dyes
Authors: Peng Zhili , Zhou Yiqun , Ji Chunyu , Pardo Joel , Mintz Keenan J. , Pandey Raja R. , Chusuei Charles C. , Graham Regina M. , Yan Guiyang , Leblanc Roger M.
Published: August 2020

Carbon dots (C-dots) were facilely fabricated via a hydrothermal method and fully characterized. Our study shows that the as-synthesized C-dots are nontoxic, negatively charged spherical particles (average diameter 4.7 nm) with excellent water dispersion ability. Furthermore, the C-dots have a rich presence of surface functionalities such as hydroxyls and carboxyls as well as amines. The significance of the C-dots as highly efficient photocatalysts for rhodamine B (RhB) and methylene blue (MB) degradation was explored. The C-dots demonstrate excellent photocatalytic activity, achieving 100% of RhB and MB degradation within 170 min. The degradation rate constants for RhB and MB were 1.8 × 10−2 and 2.4 × 10−2 min−1, respectively. The photocatalytic degradation performances of the C-dots are comparable to those metal-based photocatalysts and generally better than previously reported C-dots photocatalysts. Collectively considering the excellent photocatalytic activity toward organic dye degradation, as well as the fact that they are facilely synthesized with no need of further doping, compositing, and tedious purification and separation, the C-dots fabricated in this work are demonstrated to be a promising alternative for pollutant degradation and environment protection.
Therapeutic Manipulation of Macrophages Using Nanotechnological Approaches for the Treatment of Osteoarthritis
Authors: Ummarino Aldo , Gambaro Francesco Manlio , Kon Elizaveta , Torres Andón Fernando
Published: August 2020

Osteoarthritis (OA) is the most common joint pathology causing severe pain and disability. Macrophages play a central role in the pathogenesis of OA. In the joint microenvironment, macrophages with an M1-like pro-inflammatory phenotype induce chronic inflammation and joint destruction, and they have been correlated with the development and progression of the disease, while the M2-like anti-inflammatory macrophages support the recovery of the disease, promoting tissue repair and the resolution of inflammation. Nowadays, the treatment of OA in the clinic relies on systemic and/or intra-articular administration of anti-inflammatory and pain relief drugs, as well as surgical interventions for the severe cases (i.e., meniscectomy). The disadvantages of the pharmacological therapy are related to the chronic nature of the disease, requiring prolonged treatments, and to the particular location of the pathology in joint tissues, which are separated anatomical compartments with difficult access for the drugs. To overcome these challenges, nanotechnological approaches have been investigated to improve the delivery of drugs toward macrophages into the diseased joint. This strategy may offer advantages by reducing off-target toxicities and improving long-term therapeutic efficacy. In this review, we describe the nanomaterial-based approaches designed so far to directly or indirectly manipulate macrophages for the treatment of osteoarthritis.
Assessment of Cytokine-Induced Neutrophil Chemoattractants as Biomarkers for Prediction of Pulmonary Toxicity of Nanomaterials
Authors: Tomonaga Taisuke , Izumi Hiroto , Oyabu Takako , Lee Byeong-Woo , Kubo Masaru , Shimada Manabu , Noguchi Shingo , Nishida Chinatsu , Yatera Kazuhiro , Morimoto Yasuo
Published: August 2020

This work determines whether cytokine-induced neutrophil chemoattractants (CINC)-1, CINC-2 and CINC-3 can be markers for predicting high or low pulmonary toxicity of nanomaterials (NMs). We classified NMs of nickel oxide (NiO) and cerium dioxide (CeO2) into high toxicity and NMs of two types of titanium dioxides (TiO2 (P90 and rutile)) and zinc oxide (ZnO) into low toxicity, and we analyzed previous data of CINCs in bronchoalveolar lavage fluid (BALF) of rats from three days to six months after intratracheal instillation (0.2 and 1.0 mg) and inhalation exposure (0.32–10.4 mg/m3) of materials (NiO, CeO2, TiO2 (P90 and rutile), ZnO NMs and micron-particles of crystalline silica (SiO2)). The concentration of CINC-1 and CINC-2 in BALF had different increase tendency between high and low pulmonary toxicity of NMs and correlated with the other inflammatory markers in BALF. However, CINC-3 increased only slightly in a dose-dependent manner compared with CINC-1 and CINC-2. Analysis of receiver operating characteristics for the toxicity of NMs by CINC-1 and CINC-2 showed the most accuracy of discrimination of the toxicity at one week or one month after exposure and CINC-1 and CINC-2 in BALF following intratracheal instillation of SiO2 as a high toxicity could accurately predict the toxicity at more than one month after exposure. These data suggest that CINC-1 and CINC-2 may be useful biomarkers for the prediction of pulmonary toxicity of NMs relatively early in both intratracheal instillation and inhalation exposure.
Iron Oxide Nanoparticles as an Alternative to Antibiotics Additive on Extended Boar Semen
Authors: Tsakmakidis Ioannis A. , Samaras Theodoros , Anastasiadou Sofia , Basioura Athina , Ntemka Aikaterini , Michos Ilias , Simeonidis Konstantinos , Karagiannis Isidoros , Tsousis Georgios , Angelakeris Mavroeidis , Boscos Constantin M.
Published: August 2020

This study examined the effect of Fe3O4 nanoparticles on boar semen. Beltsville thawing solution without antibiotics was used to extend ejaculates from 5 boars (4 ejaculates/boar). Semen samples of control group (C) and group with Fe3O4 (Fe; 0.192 mg/mL semen) were incubated under routine boar semen storage temperature (17 °C) for 0.5 h and nanoparticles were removed by a magnetic field. Before and after treatment, aliquots of all groups were cultured using standard microbiological methods. The samples after treatment were stored (17 °C) for 48 h and sperm parameters (computer-assisted sperm analyzer (CASA) variables; morphology; viability; hypo-osmotic swelling test (HOST); DNA integrity) were evaluated at storage times 0, 24, 48 h. Semen data were analyzed by a repeated measures mixed model and microbial data with Student’s t-test for paired samples. Regarding CASA parameters, Fe group did not differ from C at any time point. In group C, total motility after 24 h and progressive motility after 48 h of storage decreased significantly compared to 0 h. In group Fe, linearity (LIN) after 48 h and head abnormalities after 24 h of storage increased significantly compared to 0 h. The microbiological results revealed a significant reduction of the bacterial load in group Fe compared to control at both 24 and 48 h. In conclusion, the use of Fe3O4 nanoparticles during semen processing provided a slight anti-microbiological effect with no adverse effects on sperm characteristics.
Spectral-Time Multiplexing in FRET Complexes of AgInS2/ZnS Quantum Dot and Organic Dyes
Authors: Kuznetsova Vera , Tkach Anton , Cherevkov Sergei , Sokolova Anastasiia , Gromova Yulia , Osipova Viktoria , Baranov Mikhail , Ugolkov Valery , Fedorov Anatoly , Baranov Alexander
Published: August 2020

Nowadays, multiplex analysis is very popular, since it allows to detect a large number of biomarkers simultaneously. Traditional multiplex analysis is usually based on changes of photoluminescence (PL) intensity and/or PL band spectral positions in the presence of analytes. Using PL lifetime as an additional parameter might increase the efficiency of multiplex methods. Quantum dots (QDs) can be used as luminescent markers for multiplex analysis. Ternary in-based QDs are a great alternative to the traditional Cd-based one. Ternary QDs possess all advantages of traditional QDs, including tunable photoluminescence in visible range. At the same time ternary QDs do not have Cd-toxicity, and moreover they possess long spectral dependent lifetimes. This allows the use of ternary QDs as a donor for time-resolved multiplex sensing based on Förster resonance energy transfer (FRET). In the present work, we implemented FRET from AgInS2/ZnS ternary QDs to cyanine dyes absorbing in different spectral regions of QD luminescence with different lifetimes. As the result, FRET-induced luminescence of dyes differed not only in wavelengths but also in lifetimes of luminescence, which can be used for time-resolved multiplex analysis in biology and medicine.
Nanostructured Cellulose-Based Sorbent Materials for Water Decontamination from Organic Dyes
Authors: Riva Laura , Pastori Nadia , Panozzo Alice , Antonelli Manuela , Punta Carlo
Published: August 2020

Nanostructured materials have been recently proposed in the field of environmental remediation. The use of nanomaterials as building blocks for the design of nano-porous micro-dimensional systems is particularly promising since it can overcome the (eco-)toxicological risks associated with the use of nano-sized technologies. Following this approach, we report here the application of a nanostructured cellulose-based material as sorbent for effective removal of organic dyes from water. It consists of a micro- and nano-porous sponge-like system derived by thermal cross-linking among (2,2,6,6-Tetramethylpiperidin-1-yl)oxyl (TEMPO)-oxidized cellulose nanofibers (TOCNF), branched polyethylenimine 25 kDa (bPEI), and citric acid (CA). The sorbent efficiency was tested for four different organic dyes commonly used for fabric printing (Naphthol Blue Black, Orange II Sodium Salt, Brilliant Blue R, Cibacron Brilliant Yellow), by conducting both thermodynamic and kinetic studies. The material performance was compared with that of an activated carbon, commonly used for this application, in order to highlight the potentialities and limits of this biomass-based new material. The possibility of regeneration and reuse of the sorbent was also investigated.
A Comparison of Intermittent and Continuous Exercise Bouts at Different Intensities on Appetite and Postprandial Metabolic Responses in Healthy Men
Authors: R Mattin Lewis , J McIver Victoria , Yau Adora Mo Wah , J James Lewis , H Evans Gethin
Published: August 2020

Exercise intensity affects many potential postprandial responses, but there is limited information on the influence of exercise modality. Therefore, the aim of this study was to investigate if the nature of exercise at two different intensities would affect gastric emptying rate (GER), appetite and metabolic responses following ingestion of a semi-solid meal. Twelve healthy men completed, in a random order, four 60-min cycles at 60% VO2peak (MOD), 40% VO2peak (LOW) and in a continuous (CON) or intermittent (INT) manner. INT consisted of 20 × 1-min exercise bouts with 2-min rest breaks. INT and CON were matched for total work output at each intensity. GER of the post-exercise meal was measured for 2 h using the 13C-breath method. Blood glucose, substrate utilisation and appetite ratings were measured at regular intervals throughout all trials and 24-h energy intake (EI) post-trials was assessed. GER-Delta over Baseline (DOB) was lower (p < 0.05) on MOD-INT vs. MOD-CON from 30–120 min post-meal. Blood glucose was higher mid-exercise (p < 0.05) on MOD-INT vs. MOD-CON. Although post-exercise LOW-CON was significantly higher than LOW-INT (p < 0.05), blood glucose was also higher 30-min post-meal ingestion on both CON trials compared to INT (p < 0.001). No interaction effect was observed for perceived appetite responses 2 h after meal ingestion (all p > 0.05). 24-h post-trial EI was similar between LOW-CON vs. LOW-INT (p > 0.05), although MOD-INT vs. MOD-CON 3500 ± 1419 vs. 2556 ± 989 kCal: p < 0.001 was elevated. In summary, MOD-INT exercise delays GER without stimulating perceived appetite in the 2 h period after meal ingestion, although EI was greater in the 24-h post-trial.
Dietary Advanced Glycation End-Products (dAGEs) Intake and Bone Health: A Cross-Sectional Analysis in the Rotterdam Study
Authors: Waqas Komal , Chen Jinluan , van der Eerden Bram C. J. , Ikram M. Arfan , Uitterlinden André G. , Voortman Trudy , Zillikens M. Carola
Published: August 2020

Animal studies suggest a role for dietary advanced glycation end-products (dAGEs) in bone health, but human studies on dAGEs in relation to bone are lacking. We aimed to study whether dAGEs intake is associated with the parameters of bone strength namely, bone mineral density (BMD), prevalent vertebral (VFs), and major osteoporotic fractures (MOFs = hip, wrist, proximal humerus, and clinical VFs). 3949 participants (mean age 66.7 ± 10.5 years) were included from a Rotterdam study for whom Carboxymethyllysine (CML—a dietary AGE) was estimated from food frequency questionnaires combined with dAGEs databases. Multivariable linear and logistic regression models were performed adjusting for age, sex, energy intake, dietary quality, physical activity, diabetes, smoking, renal function, and cohort effect and for models on fractures, subsequently for BMD. We observed no association of CML with BMD at both femoral neck (β = −0.006; p = 0.70) and lumbar spine (β = −0.013; p = 0.38). A higher intake of CML was linearly associated with VFs (Odds ratio, OR = 1.16, 95% CI (1.02–1.32) and a similar but non-significant trend with MOFs (OR = 1.12 (0.98–1.27). Additional adjustment for BMD did not change the associations. Our results imply a positive association between dietary intake of CML and VFs independent of BMD. Future studies are needed in order to elucidate whether associations found are causal.
Mechanism of Action of Ketogenic Diet Treatment: Impact of Decanoic Acid and Beta—Hydroxybutyrate on Sirtuins and Energy Metabolism in Hippocampal Murine Neurons
Authors: Dabke Partha , Das Anibh M.
Published: August 2020

The ketogenic diet (KD), a high-lipid and low-carbohydrate diet, has been used in the treatment of epilepsy, neurodegenerative disorders, inborn errors of metabolism and cancer; however, the exact mechanism/s of its therapeutic effect is not completely known. We hypothesized that sirtuins (SIRT)—a group of seven NAD-dependent enzymes and important regulators of energy metabolism may be altered under KD treatment. HT22 hippocampal murine neurons were incubated with two important KD metabolites–beta-hydroxybutyrate (BHB) (the predominant ketone body) and decanoic acid (C10), both accumulating under KD. Enzyme activity, protein, and gene expressions of SIRT 1-4, enzyme capacities of the mitochondrial respiratory chain complexes (MRC), citrate synthase (CS) and gene expression of monocarboxylate transporters were measured in control (untreated) and KD-treated cells. Incubation with both–BHB and C10 resulted in significant elevation of SIRT1 enzyme activity and an overall upregulation of the MRC. C10 incubation showed prominent increases in maximal activities of complexes I + III and complex IV of the MRC and ratios of their activities to that of CS, pointing towards a more efficient functioning of the mitochondria in C10-treated cells.
Ginseng Extracts, GS-KG9 and GS-E3D, Prevent Blood–Brain Barrier Disruption and Thereby Inhibit Apoptotic Cell Death of Hippocampal Neurons in Streptozotocin-Induced Diabetic Rats
Authors: Lee Jee , Park Chan , Choi Hae , Chung Sung , Pyo Mi , Yune Tae
Published: August 2020

Type 1 diabetes mellitus is known to be linked to the impairment of blood–brain barrier (BBB) integrity following neuronal cell death. Here, we investigated whether GS-KG9 and GS-E3D, bioactive ginseng extracts from Korean ginseng (Panax ginseng Meyer), inhibit BBB disruption following neuronal death in the hippocampus in streptozotocin-induced diabetic rats showing type 1-like diabetes mellitus. GS-KG9 and GS-E3D (50, 150, or 300 mg/kg, twice a day for 4 weeks) administered orally showed antihyperglycemic activity in a dose-dependent manner and significantly attenuated the increase in BBB permeability and loss of tight junction proteins. GS-KG9 and GS-E3D also inhibited the expression and activation of matrix metalloproteinase-9 and the infiltration of macrophages into the brain parenchyma, especially into the hippocampal region. In addition, microglia and astrocyte activation in the hippocampus and the expression of proinflammatory mediators such as tnf-α, Il-1β, IL-6, cox-2, and inos were markedly alleviated in GS-KG9 and GS-E3D-treated group. Furthermore, apoptotic cell death of hippocampal neurons, especially in CA1 region, was significantly reduced in GS-KG9 and GS-E3D-treated groups as compared to vehicle control. These results suggest that GS-KG9 and GS-E3D effectively prevent apoptotic cell death of hippocampal neurons by inhibiting BBB disruption and may be a potential therapy for the treatment of diabetic patients.
Nutritional Quality and Health Effects of Low Environmental Impact Diets: The “Seguimiento Universidad de Navarra” (SUN) Cohort
Authors: Fresán Ujué , Craig Winston J. , Martínez-González Miguel A. , Bes-Rastrollo Maira
Published: August 2020

Current dietary patterns are negatively affecting both the environment and people’s health. Healthy diets are generally more environmentally friendly. However, few studies have focused on the health consequences of diets with low environmental impact. We analyzed differences in the dietary composition (types of food, macro- and micro-nutrients) of those diets with high and low environmental impact, according to greenhouse gas emission and resources use (water, land and energy) using data from a Spanish cohort (17,387 participants), collected by means of a validated food frequency questionnaire. Cox analyses were used to assess the association of dietary environmental impact with total mortality risk. At a given level of energy intake, diets with lower environmental impact contained higher amounts of plant-based foods and lower levels of animal-derived products. Less polluting diets involved higher amounts of polyunsaturated fats and dietary fiber and lower amounts of saturated fats and sodium. However, diets associated with less environmental damage also contained more added sugars, but lower levels of vitamin B12, zinc and calcium. We did not detect any association between dietary environmental impact and risk of mortality. Diets should not only produce minimal environmental impact, but the maximum overall benefits for all key dimensions encompassed in sustainable diets.
Physicochemical Compatibility Investigation of Mesalazine and Folic Acid Using Chromatographic and Thermoanalytical Techniques
Authors: Jeličić Mario-Livio , Brusač Edvin , Amidžić Klarić Daniela , Nigović Biljana , Keser Sabina , Mornar Ana
Published: August 2020

Inflammatory bowel disease is a common name for Crohn’s disease and ulcerative colitis. These inflammatory states cause damage in the sidewalls of the gastrointestinal tract, resulting in malabsorption of food and vitamins. Folic acid (Vitamin B9) is often associated with inflammatory bowel diseases since reduced overall folate concentration in the human body may lead to the development of colorectal cancer and megaloblastic anaemia. However, its deficiency is easily compensated by taking an additional folic acid pill during regular therapy. At the moment, there are no studies that have examined the compatibility of folic acid with 5-aminosalicylate drugs used in the treatment of inflammatory bowel diseases. In this work, differential scanning calorimetry, forced degradation studies, isothermal stress testing and dissolution stability testing were used to determine the stability of folic acid and one of the most commonly used 5-aminosalicylates, mesalazine, when present in the same solution or blend. To monitor the assay of folic acid, mesalazine and nine of its related impurities, a single HPLC method was developed. Results of compatibility studies showed that no physicochemical interaction between mesalazine and folic acid occurs when combined, opening the path to the development of new formulations, such as a mesalazine/folic acid fixed-dose combination.
Development and Characterization of Orally Disintegrating Tablets Containing a Captopril-Cyclodextrin Complex
Authors: Musuc Adina Magdalena , Anuta Valentina , Atkinson Irina , Popa Vlad Tudor , Sarbu Iulian , Mircioiu Constantin , Abdalrb Ghaleb Abdalameer , Mitu Mirela Adriana , Ozon Emma Adriana
Published: August 2020

Captopril is the first angiotensin I-converting enzyme inhibitor widely used for the treatment of hypertension. Based on the well-known benefits of cyclodextrin inclusion complexes, the present study investigated the ability of β-cyclodextrin to include captopril. Solid inclusion complexes of captopril with β–cyclodextrin in a 1:2 molar ratio were prepared by using the paste method of complexation. For comparison purposes, a simple physical mixture with the same molar ratio was also prepared. Fourier-transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and simultaneous thermal analysis were used to characterize the raw materials, physical mixture and solid inclusion complex. In order to provide the drug in a more accessible and patient-compliant form following masking its bitter taste, as well as ensuring the appropriate release kinetics, the investigated complex was formulated as orally disintegrating tablets. The study of captopril dissolution in both compendial and simulated saliva media suggested the Noyes Whitney model as the best mathematical model to describe the release phenomena. A clinical study on healthy volunteers also highlighted the taste improvement of the new formulation as compared to conventional tablets.
Molecular Interactions in Solid Dispersions of Poorly Water-Soluble Drugs
Authors: Tran Thao T. D. , Tran Phuong H. L.
Published: August 2020

Physicochemical characterization is a crucial step for the successful development of solid dispersions, including the determination of drug crystallinity and molecular interactions. Typically, the detection of molecular interactions will assist in the explanation of different drug performances (e.g., dissolution, solubility, stability) in solid dispersions. Various prominent reviews on solid dispersions have been reported recently. However, there is still no overview of recent techniques for evaluating the molecular interactions that occur within solid dispersions of poorly water-soluble drugs. In this review, we aim to overview common methods that have been used for solid dispersions to identify different bond formations and forces via the determination of interaction energy. In addition, a brief background on the important role of molecular interactions will also be described. The summary and discussion of methods used in the determination of molecular interactions will contribute to further developments in solid dispersions, especially for quick and potent drug delivery applications.
Acceptability in the Older Population: The Importance of an Appropriate Tablet Size
Authors: Vallet Thibault , Michelon Hugues , Orlu Mine , Jani Yogini , Leglise Patrick , Laribe-Caget Sandra , Piccoli Matthieu , Le Fur Aurélie , Liu Fang , Ruiz Fabrice , Boudy Vincent
Published: August 2020

Presenting many advantages, solid oral dosage forms (SODFs) are widely manufactured and frequently prescribed in older populations regardless of the specific characteristics of patients. Commonly, patients with dysphagia (swallowing disorders) experience difficulties taking SODFs, which may lead to non-adherence or misuse. SODF characteristics (e.g., size, shape, thickness) are likely to influence swallowability. Herein, we used the acceptability reference framework (the ClinSearch acceptability score test (CAST))—a 3D-map juxtaposing two acceptability profiles—to investigate the impact of tablet size on acceptability. We collected 938 observer reports on the tablet intake by patients ≥65 years in hospitals or care homes. As we might expect, tablets could be classified as accepted in older patients without dysphagia (n = 790), while not in those with swallowing disorders (n = 146). However, reducing the tablet size had a significant impact on acceptability in this subpopulation: tablets <6.5 mm appeared to be accepted by patients with swallowing disorders. Among the 309 distinct tablets assessed in this study, ranging in size from 4.7 to 21.5 mm, 83% are ≥6.5 mm and consequently may be poorly accepted by institutionalized older people and older inpatients suffering from dysphagia. This underlines the need to develop and prescribe medicines with the best adapted characteristics to reach an optimal acceptability in targeted users.
Uptake Study in Lysosome-Enriched Fraction: Critical Involvement of Lysosomal Trapping in Quinacrine Uptake but Not Fluorescence-Labeled Verapamil Transport at Blood-Retinal Barrier
Authors: Kubo Yoshiyuki , Yamada Miki , Konakawa Saki , Akanuma Shin-ichi , Hosoya Ken-ichi
Published: August 2020

Lysosomal trapping at the blood–retinal barrier (BRB) was investigated through quinacrine and fluorescence-labeled verapamil (EFV) uptake. Quinacrine uptake by conditionally immortalized rat retinal capillary endothelial (TR-iBRB2) cells suggested saturable and non-saturable transport processes in the inner BRB. The reduction of quinacrine uptake by bafilomycin A1 suggested quinacrine distribution to the acidic intracellular compartments of the inner BRB, and this notion was also supported in confocal microscopy. In the study using the lysosome-enriched fraction of TR-iBRB2 cells, quinacrine uptake was inhibited by bafilomycin A1, suggesting the lysosomal trapping of quinacrine in the inner BRB. Pyrilamine, clonidine, and nicotine had no effect on quinacrine uptake, suggesting the minor role of lysosomal trapping in their transport across the inner BRB. Bafilomycin A1 had no effect on EFV uptake, and lysosomal trapping driven by the acidic interior pH was suggested as a minor mechanism for EFV transport in the inner BRB. The minor contribution of lysosomal trapping was supported by the difference in inhibitory profiles between EFV and quinacrine uptakes. Similar findings were observed in the outer BRB study with the fraction of conditionally immortalized rat retinal pigment epithelial (RPE-J) cells. These results suggest the usefulness of lysosome-enriched fractions in studying lysosomal trapping at the BRB.
Nanoparticles Formulations of Artemisinin and Derivatives as Potential Therapeutics for the Treatment of Cancer, Leishmaniasis and Malaria
Authors: Alven Sibusiso , Aderibigbe Blessing Atim
Published: August 2020

Cancer, malaria, and leishmaniasis remain the deadly diseases around the world although several strategies of treatment have been developed. However, most of the drugs used to treat the aforementioned diseases suffer from several pharmacological limitations such as poor pharmacokinetics, toxicity, drug resistance, poor bioavailability and water solubility. Artemisinin and its derivatives are antimalarial drugs. However, they also exhibit anticancer and antileishmanial activity. They have been evaluated as potential anticancer and antileishmanial drugs but their use is also limited by their poor water solubility and poor bioavailability. To overcome the aforementioned limitations associated with artemisinin and its derivatives used for the treatment of these diseases, they have been incorporated into nanoparticles. Several researchers incorporated this class of drugs into nanoparticles resulting in enhanced therapeutic outcomes. Their potential efficacy for the treatment of parasitic infections such as malaria and leishmaniasis and chronic diseases such as cancer has been reported. This review article will be focused on the nanoparticles formulations of artemisinin and derivatives for the treatment of cancer, malaria, and leishmaniasis and the biological outcomes (in vitro and in vivo).
A Student Pharmacist Quality Engagement Team to Support Initial Implementation of Comprehensive Medication Management within Independent Community Pharmacies
Authors: Herbert Sophia M. C. , Carroll Joni C. , Coley Kim C. , McGrath Stephanie Harriman , McGivney Melissa Somma
Published: August 2020

In 2017, the Pennsylvania Pharmacists Care Network (PPCN), an enhanced pharmacy services network, and STRAND Clinical Technologies partnered to launch a payor contract with a Pennsylvania Medicaid Managed Care Organization for the provision of comprehensive medication management (CMM) at PPCN pharmacies. PPCN and the Community Leadership and Innovation in Practice Center at the University of Pittsburgh School of Pharmacy partnered to create the Quality Engagement Team (QET), a group of student pharmacists formed with the intent to support the initial implementation of this contract. The QET supported the pharmacies through biweekly phone calls, which led to increased pharmacist engagement and produced impactful patient encounter stories that were then reported back to the payor. We utilized Active Implementation Frameworks and select implementation strategies from the Expert Recommendations for Implementing Change project throughout the implementation period. The QET supported the successful implementation of this payor contract, which saw an increase in CMM encounters completed by the pharmacists during each month of the four-month contract period. Students, pharmacists and the payor each derived meaningful benefits from this initiative. Student pharmacists can be a powerful asset in the implementation of payor programs within an enhanced pharmacy services network, resulting in the mutually beneficial and sustainable support of the network.
Mechanical Stress Inhibits Early Stages of Endogenous Cell Migration: A Pilot Study in an Ex Vivo Osteochondral Model
Authors: Vainieri Maria L. , Alini Mauro , Yayon Avner , van Osch Gerjo J. V. M. , Grad Sibylle
Published: August 2020

Cell migration has a central role in osteochondral defect repair initiation and biomaterial-mediated regeneration. New advancements to reestablish tissue function include biomaterials and factors promoting cell recruitment, differentiation and tissue integration, but little is known about responses to mechanical stimuli. In the present pilot study, we tested the influence of extrinsic forces in combination with biomaterials releasing chemoattractant signals on cell migration. We used an ex vivo mechanically stimulated osteochondral defect explant filled with fibrin/hyaluronan hydrogel, in presence or absence of platelet-derived growth factor-BB or stromal cell-derived factor 1, to assess endogenous cell recruitment into the wound site. Periodic mechanical stress at early time point negatively influenced cell infiltration compared to unloaded samples, and the implementation of chemokines to increase cell migration was not efficient to overcome this negative effect. The gene expression at 15 days of culture indicated a marked downregulation of matrix metalloproteinase (MMP)13 and MMP3, a decrease of β1 integrin and increased mRNA levels of actin in osteochondral samples exposed to complex load. This work using an ex vivo osteochondral mechanically stimulated advanced platform demonstrated that recurrent mechanical stress at early time points impeded cell migration into the hydrogel, providing a unique opportunity to improve our understanding on management of joint injury.
Ionic Liquid-Incorporated Zn-Ion Conducting Polymer Electrolyte Membranes
Authors: Liu Jianghe , Ahmed Sultan , Khanam Zeba , Wang Ting , Song Shenhua
Published: August 2020

In this study, novel ionic liquid-incorporated Zn-ion conducting polymer electrolyte membranes containing polymer matrix poly (vinylidene fluoride-hexafluoropropylene) (PVdF-HFP) and 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMITf), along with zinc trifluoromethanesulfonate Zn(Tf)2, are prepared and investigated. It is ascertained that the optimal membrane ILPE-Zn-4 (the mass ratio of EMITf:Zn(Tf)2:PVDF-HFP is 0.4:0.4:1), with abundant nanopores, exhibits a high amorphousness. At room temperature, the optimized electrolyte membrane offers a good value of ionic conductivity (~1.44 × 10−4 S cm−1), with a wide electrochemical stability window (~4.14 V). Moreover, the electrolyte membrane can sustain a high thermal decomposition temperature (~305 °C), and thus its mechanical performance is sufficient for practical applications. Accordingly, the ionic liquid-incorporated Zn-ion conducting polymer electrolyte could be a potential candidate for Zn-based energy storage applications.
Crystallization Induced Enhanced Emission in Two New Zn(II) and Cd(II) Supramolecular Coordination Complexes with the 1-(3,4-Dimethylphenyl)-5-Methyl-1H-1,2,3-Triazole-4-Carboxylate Ligand
Authors: Narea Pilar , Cisterna Jonathan , Cárdenas Alejandro , Amo-Ochoa Pilar , Zamora Félix , Climent Clàudia , Alemany Pere , Conejeros Sergio , Llanos Jaime , Brito Iván
Published: August 2020

Two new d10 metal supramolecular metal–organic frameworks (SMOFs) with general formula [ML2(H2O)2]n (M = Zn, Cd) have been synthetized using the sodium salt of the anionic 1-(3,4-dimethylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylate ligand (Na+L−). Both SMOFs have been structurally characterized by single-crystal X-ray diffraction analysis and IR spectroscopy. The compounds are isostructural and form supramolecular aggregates via hydrogen bonds with the presence of less common dihydrogen bonds. Interestingly, they show ionic conductivity and porosity. The luminescent properties have been also studied by means of the excitation and emission spectra. Periodic DFT and molecular TD-DFT calculations have been used to unravel the emergence of luminescence in the otherwise non-emitting 1-(3,4-dimethylphenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylate ligand once incorporated in the SMOFs. Our results also illustrate the importance of considering the dielectric environment in the crystal when performing excited state calculations for isolated fragments to capture the correct electronic character of the low-lying states, a practice which is not commonly adopted in the community.
Microfluidic Fabrication of Click Chemistry-Mediated Hyaluronic Acid Microgels: A Bottom-Up Material Guide to Tailor a Microgel’s Physicochemical and Mechanical Properties
Authors: Heida Thomas , Otto Oliver , Biedenweg Doreen , Hauck Nicolas , Thiele Julian
Published: August 2020

The demand for tailored, micrometer-scaled biomaterials in cell biology and (cell-free) biotechnology has led to the development of tunable microgel systems based on natural polymers, such as hyaluronic acid (HA). To precisely tailor their physicochemical and mechanical properties and thus to address the need for well-defined microgel systems, in this study, a bottom-up material guide is presented that highlights the synergy between highly selective bio-orthogonal click chemistry strategies and the versatility of a droplet microfluidics (MF)-assisted microgel design. By employing MF, microgels based on modified HA-derivates and homobifunctional poly(ethylene glycol) (PEG)-crosslinkers are prepared via three different types of click reaction: Diels–Alder [4 + 2] cycloaddition, strain-promoted azide-alkyne cycloaddition (SPAAC), and UV-initiated thiol–ene reaction. First, chemical modification strategies of HA are screened in-depth. Beyond the microfluidic processing of HA-derivates yielding monodisperse microgels, in an analytical study, we show that their physicochemical and mechanical properties—e.g., permeability, (thermo)stability, and elasticity—can be systematically adapted with respect to the type of click reaction and PEG-crosslinker concentration. In addition, we highlight the versatility of our HA-microgel design by preparing non-spherical microgels and introduce, for the first time, a selective, hetero-trifunctional HA-based microgel system with multiple binding sites. As a result, a holistic material guide is provided to tailor fundamental properties of HA-microgels for their potential application in cell biology and (cell-free) biotechnology.
Halloysite Nanotubes Coated by Chitosan for the Controlled Release of Khellin
Authors: Lisuzzo Lorenzo , Cavallaro Giuseppe , Milioto Stefana , Lazzara Giuseppe
Published: August 2020

In this work, we have developed a novel strategy to prepare hybrid nanostructures with controlled release properties towards khellin by exploiting the electrostatic interactions between chitosan and halloysite nanotubes (HNT). Firstly, khellin was loaded into the HNT lumen by the vacuum-assisted procedure. The drug confinement within the halloysite cavity has been proved by water contact angle experiments on the HNT/khellin tablets. Therefore, the loaded nanotubes were coated with chitosan as a consequence of the attractions between the cationic biopolymer and the halloysite outer surface, which is negatively charged in a wide pH range. The effect of the ionic strength of the aqueous medium on the coating efficiency of the clay nanotubes was investigated. The surface charge properties of HNT/khellin and chitosan/HNT/khellin nanomaterials were determined by ζ potential experiments, while their morphology was explored through Scanning Electron Microscopy (SEM). Water contact angle experiments were conducted to explore the influence of the chitosan coating on the hydrophilic/hydrophobic character of halloysite external surface. Thermogravimetry (TG) experiments were conducted to study the thermal behavior of the composite nanomaterials. The amounts of loaded khellin and coated chitosan in the hybrid nanostructures were estimated by a quantitative analysis of the TG curves. The release kinetics of khellin were studied in aqueous solvents at different pH conditions (acidic, neutral and basic) and the obtained data were analyzed by the Korsmeyer–Peppas model. The release properties were interpreted on the basis of the TG and ζ potential results. In conclusion, this study demonstrates that halloysite nanotubes wrapped by chitosan layers can be effective as drug delivery systems.
Strength of Flocs Formed by the Complexation of Lysozyme with Leonardite Humic Acid
Authors: Wan Abdul Khodir Wan Khairunnisa , Hakim Azizul , Kobayashi Motoyoshi
Published: August 2020

Aggregation and aggregates properties of natural organic and nanosized macromolecules such as humic substances and proteins are crucial to explore so-called colloid-mediated transport and the fate of substances in soil and water environments. Therefore, the aggregation and dispersion, charging, and floc strength of lysozyme (LSZ)–leonardite humic acid (LHA) flocs were experimentally investigated. The experiments were performed in different salt concentrations and LSZ to LHA mass ratios as a function of pH. We obtained the stronger flocs at pH 4.4, where the isoelectric point (IEP) of the complex with the mass ratio 2.5 was confirmed. Thus, the aggregation of LSZ–LHA flocs is mainly caused by charge neutralization. We obtained the floc strength of 4.7 nN around IEP at low salt concentration of 3 mM, which was stronger than 2.8 nN in high salt concentration of 50 mM. The effect of salt concentration can be rationalized by charge-patch attraction at low salt concentration. With increasing mass ratio, the IEP shifted to higher pH. This is due to the increase in positive charge from LSZ in the mixture. The effect of the LSZ to LHA mass ratio on the maximum strength was weak in the range studied.
Effect of Thermal Annealing on Conformation of MEH-PPV Chains in Polymer Matrix: Coexistence of H- and J-Aggregates
Authors: Hu Shu , Liao Yang , Zhang Yang , Yan Xiaoliang , Zhao Zhenlu , Chen Weiqiang , Zhang Xin , Liu Hongxing , Li Heng , Li Li , Sun Ming , Sheng Chuanxiang
Published: August 2020

In diluted solid solution using poly(2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene) (MEH-PPV) and polymethyl methacrylate (PMMA) or polystyrene (PS), both aggregated and extended conformations could be formed according to the weight ratio. Aggregated conformation in as-cast MEH-PPV/PMMA film presented a J-aggregate-like photoluminescence (PL) emission. After annealing at 160 °C, its PL showed characteristics of both J- and H-aggregates at the same time; however, extended conformation showed an oligomer-like emission, which was not sensitive to either measurement temperature or annealing temperature. Thus, the conformation transition between aggregated and extended is unlikely to happen in MEH-PPV/PMMA blends during thermal annealing. On the contrary, in MEH-PPV/PS blends, extended conformation dominated in as-cast film with oligomer-like emissions; after annealing at 160 °C, both J- and H- aggregate-like PL emissions were observed, indicating the conformation transitioned from extended to aggregated. Therefore, our work may suggest a new method to manipulate photophysical properties of conjugated polymers by combining appropriate host matrix and thermal annealing processes.
Promising Mechanical, Thermal, and Ballistic Properties of Novel Epoxy Composites Reinforced with Cyperus malaccensis Sedge Fiber
Authors: de Mendonça Neuba Lucas , Pereira Junio Raí , Ribeiro Matheus , Souza Andressa , de Sousa Lima Eduardo , Garcia Filho Fábio , Figueiredo André , Braga Fábio , Azevedo Afonso , Monteiro Sergio
Published: August 2020

Composites reinforced with natural lignocellulosic fibers (NLFs) are gaining relevance as the worldwide demand for renewable and sustainable materials increases. To develop novel natural composites with satisfactory properties, less common NLFs should also be investigated. Among these, the Cyperus malaccensis (CM), a type of sedge fiber, is already used in simple items like ropes, furniture, and paper, but has not yet been investigated as composite reinforcement for possible engineering applications. Therefore, the present work evaluated for the first time the properties of novel epoxy composites incorporated with 10, 20, and 30 vol.% of CM sedge fibers. Tensile, Izod-impact, and ballistic impact tests were performed, as well as Fourier transform infrared (FT-IR) spectroscopy and thermal analysis of the composites. Results disclosed a decrease (−55%) in tensile strengths as compared to the neat epoxy. However, the elastic modulus of the 30 vol.% sedge fiber composite increased (+127%). The total strain and absorbed ballistic energy did not show significant variation. The Izod impact energy of the 30 vol.% composite was found to be 181% higher than the values obtained for the neat epoxy as a control sample. An increase in both stiffness and toughness characterized a reinforcement effect of the sedge fiber. The thermal analysis revealed a slight decrease (−15%) in the degradation temperature of the CM sedge fiber composites compared to the neat epoxy. The glass-transition temperatures were determined to be in the range of 67 to 81 °C.
Nanosilica-Toughened Epoxy Resins
Authors: Sprenger Stephan
Published: August 2020

Surface-modified silica nanoparticles are available as concentrates in epoxy resins in industrial quantities for nearly 20 years. Meanwhile, they are used in many epoxy resin formulations for various applications like fiber-reinforced composites, adhesives or electronic components; even in space vehicles like satellites. Some of the drawbacks of “classic” epoxy toughening using elastomers as a second phase, like lower modulus or a loss in strength can be compensated by using nanosilica together with such tougheners. Apparently, there exists a synergy as toughness and fatigue performance are increased significantly. This work intends to provide an overview regarding the possibilities of nanotoughening with silica, the industrial applications of such epoxy resin formulations and the most recent research results.
Developed Chitosan/Oregano Essential Oil Biocomposite Packaging Film Enhanced by Cellulose Nanofibril
Authors: Chen Shunli , Wu Min , Wang Caixia , Yan Shun , Lu Peng , Wang Shuangfei
Published: August 2020

The use of advanced and eco-friendly materials has become a trend in the field of food packaging. Cellulose nanofibrils (CNFs) were prepared from bleached bagasse pulp board by a mechanical grinding method and were used to enhance the properties of a chitosan/oregano essential oil (OEO) biocomposite packaging film. The growth inhibition rate of the developed films with 2% (w/w) OEO against E. coli and L. monocytogenes reached 99%. With the increased levels of added CNFs, the fibrous network structure of the films became more obvious, as was determined by SEM and the formation of strong hydrogen bonds between CNFs and chitosan was observed in FTIR spectra, while the XRD pattern suggested that the strength of diffraction peaks and crystallinity of the films slightly increased. The addition of 20% CNFs contributed to an oxygen-transmission rate reduction of 5.96 cc/m2·day and water vapor transmission rate reduction of 741.49 g/m2·day. However, the increase in CNFs contents did not significantly improve the barrier properties of the film. The addition of 60% CNFs significantly improved the barrier properties of the film to light and exhibited the lowest light transmittance (28.53%) at 600 nm. Addition of CNFs to the chitosan/OEO film significantly improved tensile strength and the addition of 60% CNFs contributed to an increase of 16.80 MPa in tensile strength. The developed chitosan/oregano essential oil/CNFs biocomposite film with favorable properties and antibacterial activity can be used as a green, functional material in the food-packaging field. It has the potential to improve food quality and extend food shelf life.