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Statins are among the most widely used drugs for the inhibition of cholesterol biosynthesis, prevention of cardiovascular diseases, and treatment of hypercholesterolemia. Additionally, statins also exhibit cholesterol-independent benefits in various diseases, including neuroprotective properties in Alzheimer's disease, anti-inflammatory effects in coronary artery disease, and antiproliferative activities in cancer, which likely result from the statins' interaction and alteration of lipid bilayers. However, the membrane-modulatory effects of statins and the mechanisms by which statins alter lipid bilayers remain poorly understood. In this work, we explore the membrane-modulating effects of statins on model lipid bilayers and live cells. Through the use of fluorescence lifetime imaging microscopy (FLIM) combined with viscosity-sensitive environmental probes, we demonstrate that hydrophobic, but not hydrophilic, statins are capable of changing the microviscosity and lipid order in model and live cell membranes. Furthermore, we show that hydrophobic simvastatin is capable of forming nanoscale cholesterol-rich domains and homogenizing the cholesterol concentrations in lipid bilayers. Our results provide a mechanistic framework for understanding the bimodal effects of simvastatin on the lipid order and the lateral organization of cholesterol in lipid bilayers. Finally, we demonstrate that simvastatin temporarily decreases the microviscosity of live cell plasma membranes, making them more permeable and increasing the level of intracellular chemotherapeutic drug accumulation.

The alleviating role of starch derivatives on the quality deterioration of frozen steamed bread dough was investigated in terms of derivative structure, the bread characteristics and dough properties including freezable water contents, yeast activity as well as dough viscoelasticity. The addition of starch derivatives including short-clustered maltodextrin (SCMD), DE2 maltodextrin (MD) and pregelatinized starch (PGS) significantly increased the specific volume and decreased the hardness of steamed bread compared with Control bread after 8-week frozen storage. Lower freezable water content was found in PGS dough than SCMD dough, which was consistent with the results of water absorption index of starch derivatives. The analysis of dough gassing rate and yeast survival ratio demonstrated SCMD could provide more cryoprotection for yeast cells. Meanwhile, a higher elastic module and a more continuous gluten-network structure of SCMD dough were found after 8-week frozen storage. These results indicated starch derivatives especially SCMD were promising to be used as the alternative improvers in frozen dough production., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Introduction: the goal of this work was to evaluate the acceptance of various types of thickeners, specifically modified starch thickener and gum thickener, both with and without flavoring. Patients and methods: a randomized sample of 40 hospitalized patients with oropharyngeal dysphagia was recruited. The taste, smell, and appearance of each type of thickener were evaluated, as well as the volume of liquid ingested by the patients taking each type of thickener (modified starch thickener vs. gum thickener, both with and without flavoring). Results: the overall acceptance of gum thickener was significantly higher than that of modified starch thickener (7.45 (1.57) vs. 5.10 (2.43), respectively; p = 0.001). When a food flavor was added to the thickened water, the overall rating of the product was higher than when no flavor was added (7.70 (1.53) vs. 4.85 (2.16); p < 0.001). The difference between the daily volume of water consumed by the patients who received gum thickeners (928.33 (331.27) mL) and those who received starch thickeners (670.00 (288.35) mL) was statistically significant (p = 0.012). Patient consumption was also higher when flavoring was added as compared to when it was not (943.33 (302.45) mL) vs. (655.00 (304.60) mL; p = 0.005). Conclusion: the acceptances of the thickener and of water intake by patients with dysphagia were both significantly higher when using gum thickeners compared to starch thickeners, and when adding flavoring.

The viscosity of plasma and mitochondrial membranes of hepatocytes was studied in young (3-month-old) and old (9-month-old) male Wistar rats. It was shown that viscosity of hepatocyte plasma and mitochondrial membranes in young rats under optimal vital functions in the area of protein-lipid membrane contacts was significantly lower than in old rats. No age-related differences in the viscosity of lipid-lipid membrane contacts and in the polarity of protein-lipid contacts and lipid layers were found. Liver cirrhosis induced by carbon tetrachloride and ethanol administration was associated with increased fluidity of the plasma and mitochondrial membranes of hepatocytes in rats of both age groups. The decrease in membrane viscosity in young rats occurred due to a decrease of the viscosity in the area of protein-lipid and lipid-lipid contacts, while in old rats in the area of protein-lipid contacts. Carbon tetrachloride and ethanol did not affect the polarity of lipid contacts and lipid layers., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Polylactide (PLA) nanocomposites with spray-and freeze-dried cellulose nanocrystals (i.e., SCNC and FCNC) were prepared through solution casting using four different solvents: tetrahydrofuran (THF), chloroform (CHL), dimethylformamide (DMF), and dimethyl sulfoxide (DMSO). Small amplitude oscillatory shear rheological analysis was extensively employed to explore the CNC dispersion quality in PLA. Overall, the rheological properties differences of PLA/SCNC and PLA/FCNC nanocomposites were not very significant. Moreover, the use of THF and CHL did not lead to a proper dispersion of CNCs in PLA due to their low dielectric constants. On the other hand, while the use of DMF was effective on the enhancement of CNC dispersion, DMSO could more dramatically lead to such enhancement due to its higher dielectric constant. The percolation threshold in PLA/SCNC nanocomposites prepared with DMF and DMSO was predicted around 1.52 and 0.12 wt% CNC, respectively. The crystallization behavior of PLA/nanocomposites prepared with DMF and DMSO were also explored., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Topical instillation of eye drops represents the treatment of choice for many ocular diseases. Ophthalmic formulations must meet general requirements, i.e. pH, osmolality, transparency and viscosity to ensure adequate retention without inducing irritation and the development of eye infections. We developed a phosphorylated xanthan gum-Ag(I) complex (XGP-Ag) showing pH (pH = 7.1 ± 0.3) and osmolality values (311 ± 2 mOsm/kg) close to that of human tears (pH = 6.5-7.6 and 304 ± 23 mOsm/kg) thanks to the presence of phosphate moieties along the chain. The presence of phosphate groups covalently bound to the XG chains avoids their dispersion in fluid, thus reducing the risk of corneal calcification. 0.02% w/v XGP-Ag solution showed high transparency (higher than 95% along the entire visible range), adequate refractive index (1.334 ± 0.001) and viscosity in the range: γ 1 s -1 -10,000 s - 1 (26.4 ± 0.8-2.1 ± 0.4 mPa·s). Its cytotoxicity and capability to hinder bacterial proliferation was also verified., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Living tissues are non-linearly elastic materials that exhibit viscoelasticity and plasticity. Man-made, implantable bioelectronic arrays mainly rely on rigid or elastic encapsulation materials and stiff films of ductile metals that can be manipulated with microscopic precision to offer reliable electrical properties. In this study, we have engineered a surface microelectrode array that replaces the traditional encapsulation and conductive components with viscoelastic materials. Our array overcomes previous limitations in matching the stiffness and relaxation behaviour of soft biological tissues by using hydrogels as the outer layers. We have introduced a hydrogel-based conductor made from an ionically conductive alginate matrix enhanced with carbon nanomaterials, which provide electrical percolation even at low loading fractions. Our combination of conducting and insulating viscoelastic materials, with top-down manufacturing, allows for the fabrication of electrode arrays compatible with standard electrophysiology platforms. Our arrays intimately conform to the convoluted surface of the heart or brain cortex and offer promising bioengineering applications for recording and stimulation., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

An oxovanadium(IV) - curcumin based complex, viz. [VO(cur)(2,2´-bipy)(H 2 O)] where cur is curcumin and bipy is bipyridine, previously synthesized, has been studied for interaction with albumin and DNA. Fluorescence emission spectroscopy was used to evaluate the interaction of the complex with bovine serum albumin (BSA) and the BSA-binding constant (K b ) was calculated to be 2.56 x 10 5 M -1 , whereas a single great-affinity binding site was revealed. Moreover, the hemocompatibility test demonstrated that the complex presented low hemolytic fraction (mostly below 1%), in all concentrations tested (0-250 μΜ of complex, 5% DMSO) assuring a safe application in interaction with blood. The binding of the complex to DNA was also investigated using absorption, fluorescence, and viscometry methods indicating a binding through a minor groove mode. From competitive studies with ethidium bromide the apparent binding constant value to DNA was estimated to be 4.82 x 10 6 M -1 . Stern-Volmer quenching phenomenon gave a Κ SV constant [1.92 (± 0.05) x 10 4 M -1 ] and k q constant [8.33 (± 0.2) x 10 11 M -1 s -1 ]. Molecular docking simulations on the crystal structure of BSA, calf thymus DNA, and DNA gyrase, as well as pharmacophore analysis for BSA target, were also employed to study in silico the ability of [VO(cur)(2,2´-bipy)(H 2 O)] to bind to these target bio-macromolecules and explain the observed in vitro activity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Measuring the solubility of a crystalline active pharmaceutical ingredient (API) in a polymer-rich system is challenging due to the high viscosity of the polymer which kinetically impedes reaching the solubility equilibrium. In this study, a rheological approach of determining the solubilizing temperature of a crystalline API in a polymeric carrier has been developed. To validate the method, a model physical mixture of crystalline posaconazole and copovidone with a relatively low API load (25 wt%) was utilized. First, a comparison between conventional differential scanning calorimetry (DSC) and a rheological temperature ramp was conducted to illustrate that the rheological method could capture the melting point depression behavior similarly to the more well-known DSC technique. Second, to further understand the dissolution process of the crystalline posaconazole into the copovidone carrier and precisely measure the solubilizing temperature, a series of isothermal rheological time sweeps were carried out at various temperatures selected based on the rheological temperature sweep. Because the dissolved API molecule imparted a plasticizing effect to the polymeric carrier, the complex viscosity of the API-polymer system decreased gradually over time and correlated well to an exponential decay function. Moreover, dependent on the applied temperature, the API-polymer system eventually accomplished distinct equilibrium states (complex viscosities) within different time frames. The obtained time constants at different temperatures were fitted to the Arrhenius equation, allowing the determination of the activation energy of the mixing process. The results indicated that once the processing temperature exceeded a critical point below the melting point of the crystalline API, the API-polymer solubilization process switched from a surface dominated dispersive mechanism to a molecular-level solubilization mode, manifested by the significantly increased activation energy. To the best of our knowledge, the currently developed rheological approach was the first successful measurement of the solubilizing temperature of a crystalline drug in a polymer-rich system., (Copyright © 2021 Elsevier B.V. All rights reserved.)

According to the Chinese traditional black jelly production process, a critical step to ensure the quality of jelly is to add alkali to it. In this study, the effects of sodium carbonate (Na 2 CO 3 ) and sodium bicarbonate (NaHCO 3 ) on the pasting, rheological, textural, and structural properties of sweet potato starch (SPS)-Mesona chinensis Benth polysaccharide (MCP) gels were evaluated. Adding Na 2 CO 3 at low concentration reduced the final viscosity (FV) of SPS-MCP gels, whereas adding it at a high concentration increased the FV. Adding NaHCO 3 can increase the FV of SPS-MCP gels in a concentration-dependent manner. Rheological results indicated that adding NaHCO 3 at a low concentration decreased the storage modulus of SPS-MCP gels, whereas adding it at a high concentration increased the storage modulus. The storage modulus of SPS-MCP gels increased with increasing concentration of NaHCO 3 . The addition of Na 2 CO 3 and NaHCO 3 improved the textural properties of SPS-MCP gels and decreased the water mobility. Infrared results indicated that adding alkali can enhance the hydrogen bonding between SPS and MCP. Scanning electron microscopy results suggested that alkali can reduce the size of gels, and make the structure more compact., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In the present study, chitosan (CS) and pectin (PEC) were utilized for the preparation of 3D printable inks through pneumatic extrusion for biomedical applications. CS is a polysaccharide with beneficial properties; however, its printing behavior is not satisfying, rendering the addition of a thickening agent necessary, i.e., PEC. The influence of PEC in the prepared inks was assessed through rheological measurements, altering the viscosity of the inks to be suitable for 3D printing. 3D printing conditions were optimized and the effect of different drying procedures, along with the presence or absence of a gelating agent on the CS-PEC printed scaffolds were assessed. The mean pore size along with the average filament diameter were measured through SEM micrographs. Interactions among the characteristic groups of the two polymers were evident through FTIR spectra. Swelling and hydrolysis measurements confirmed the influence of gelation and drying procedure on the subsequent behavior of the scaffolds. Ascribed to the beneficial pore size and swelling behavior, fibroblasts were able to survive upon exposure to the ungelated scaffolds.

A novel high-throughput aqueous solubility assay was developed for peptides and proteins exhibiting a high gelling propensity (in this case, antibacterial teixobactin analogues). By integrating the assessment of gel formation, as indicated by an increase in the solution viscosity, into the peptide equilibrium solubility screening assay, we were able to estimate the "free-flowing solubility", which is defined as the concentration at which the peptide solution not only is fully dissolved but also is a liquid exhibiting ideal flowing characteristics. In this workflow, peptide solutions passing the turbidity assessment were further screened by viscosity measurements based on nanobead-assisted dynamic light scattering analysis in a 96-well plate. The method is able to effectively detect the initiation of peptide gelation and facilitate compound ranking based on their aqueous solubility. The application of such an approach helped confirm that the substitution of Ser 3 in teixobactin led to desired physicochemical improvements and provided a focal point for further chemistry structure-activity relationship exploration.

Objectives: Dysphagia is common in patients with acute ischemic stroke patients (AIS) and it increases the risk of aspiration pneumonia after AIS. The volume-viscosity swallow test (V-VST) is a useful dysphagia screening tool. Therefore, we aim to explore the association between dysphagia (using the modified V-VST) and aspiration pneumonia in acute ischemic stroke patients., Patients and Methods: All patients with acute ischemic stroke (AIS) admitted during 1 January 2018 and 31 December 2018 were screened in this study by completing the modified V-VST within 24 hours after admission. The information of aspiration pneumonia was obtained from electronic medical system (EMS) and discharge notes., Results: Among 624 AIS patient, there were 152(24.36%) patients who suffered from aspiration pneumonia (95% CI, 20.65% - 27.35%) during hospitalization. Among all of them, patients with both impaired safety and impaired efficacy (HR, 7.53, 95%CI, 3.42-16.58, P < 0.001)) had a higher risk of aspiration pneumonia than those with only safety impaired (HR, 2.38, 95%CI, 1.40-4.04, P < 0.001) or only efficacy impaired (HR, 2.47, 95%CI, 1.33-4.57, P = 0.004). The risk of aspiration pneumonia was also associated with their completed volume at each viscosity. The patients with all impairment of three viscosities were also found to be related to the higher risk of developing aspiration pneumonia (P = 0.029)., Conclusions: The Modified V-VST is an easy-hand on, reliable screening tool for dysphagia among patients with AIS. Patient subgroup analyses based on the modified V-VST might be able to predict the risk of aspiration pneumonia during hospitalization., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Mounting evidences have recognized that dual cross-link and double-network gels can promisingly recapitulate the complex living tissue architecture and overcome mechanical limitations of conventional scaffolds used hitherto in regenerative medicine. Here, dual cross-link gels formed of a bioactive lactose-modified chitosan reticulated via both temporary (boric acid-based) and permanent (genipin-based) cross-linkers are reported. While boric acid rapidly binds to lactitol flanking diols increasing the overall viscosity, a slow temperature-driven genipin binding process takes place allowing for network strengthening. Combination of frequency and stress sweep experiments in the linear stress-strain region shows that ultimate gel strength, toughness, and viscoelasticity depend on polymer-to-genipin molar ratio. Notably, herewith it is demonstrated that linear stretching correlates with strain energy dissipation through boric acid binding/unbinding dynamics. Strain-hardening effect in the nonlinear regime, along with good biocompatibility in vitro, points at an interesting role of present system as biological extracellular matrix substitute., (© 2020 Wiley-VCH GmbH.)

In this study, starches of three mung bean cultivars (Vigna radiata) having different amylose contents were isolated and modified using a combination of citric acid and heat-moisture treatment (CA-HMT) or a combination of citric acid and annealing treatment (CA-ANN). Physicochemical properties and in vitro digestibility of native and treated mung bean starches were investigated. Resistant starch (RS) contents of the high-amylose, medium-amylose and low-amylose starches treated with CA-ANN were 41.1%, 35.7% and 27.1%, respectively, being higher than those treated with CA-HMT or native starches in the same variety. The CA-ANN did not affect the morphology and crystallinity of the starches. However, the starches treated by the CA-HMT were partly gelatinized and had higher degree of relative crystallinity as compared to the native starches. The DP¯s, swelling power, and viscosity of the treated starches were significantly lower than those of the native starches. The high-amylose mung bean starch was greatly affected by the treatments rather than medium- or low-amylose mung bean starch., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recently, biodegradable macromolecules have been highly desired as a promising alternative for traditional oil-based plastics to work out the eco crisis and biological health problems triggered by microplastics. Herein, we presented a simple, effective, environmentally friendly and CO 2 -based foaming methodology for fabricating ultra-low-density poly (lactic acid)/carbon nanotube (PLA/CNTs) nanocomposite foam. By the gradual incorporation of CNTs, three kinds of networks generated in PLA/CNTs nanocomposites and had a distinct reinforcement influence on their melt viscoelasticity, which testified by transmission electron microscope, electrical conductivity and rheological property measurements, severally. Specifically, the storage modulus of PLA/CNTs nanocomposites were 3 orders of magnitude higher in contrast to pure PLA. Interestingly, relative to that under regular differential scanning calorimetry (DSC), a double melting peak phenomenon appeared in the high-pressure DSC curves of diverse PLA specimens. Biodegradable PLA/CNTs nanocomposite foam was successfully fabricated with a super-high volume expansion ratio (VER) of 49.6 times, which could offer a promising strategy for developing other thermoplastic polyester foams with ultra-high VER to obtain some unique functional attributes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The natural starch (NS) is modified by an esterification process which is accomplished by reacting the NS and phosphate together with urea via a facile alcohol solvothermal method. After modification, a series of obvious variations can be easily confirmed for the resulted starch phosphate carbamides (denoted as SPC) compared with that of NS, such as the introduction of new groups of CO, PO, P-O-C and P-O-H together with new elements of N and P in starch molecular structure unit confirmed in FT-IR and XPS analyses and the decreased crystallinity along with formed surface defect demonstrated in XRD and SEM measurements. Furthermore, the formed SPC has a higher viscosity of 480 mPa.s -1 and lower gelatinization temperature of under 10 °C than that of the NS. More importantly, when the SPC is utilized as outer coating material together with ethylcellulose (EC) as inner coating material for preparing double-layer slow-release urea (denoted as EC/SPC based SRU), the EC/SPC based SRU has a desirable slow-release behavior with release percentages of 40.9% for 12 h in water and merely 59.6% for 20 day together with even exceeding 30 days in soil. Conclusively, this work provides a facile preparation approach for the SPC and its creative application for the preparation of SRU., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This work concerns the chemical modification of medium molecular weight hyaluronan for ophthalmic applications. The synthesis of amphiphilic HA with dodecanoyl moities was carried out under mild aqueous conditions. Perfect control of the degree of substitution was obtained by varying the molar ratio of activated fatty acid used in the reaction feed. Moreover, the preparation of the derivatives was optimized to achieve the desired degree of substitution (DS = 9.0 ± 0.2 %). The prepared hyaluronan derivatives were water-soluble and exhibited self-associating properties (amphiphilicity). The structure of the prepared derivatives was elucidated by NMR spectroscopy, rheology, turbidity, SEC-MALLS, and gas chromatography (GC). The hydrophobic moieties increase the solution viscosity by physical crosslinking. Low concentration of HAC12 is needed to prepare highly viscous solutions with potential use for ophthalmic applications. Amphiphilic HA kept the biocompatibility of hyaluronan. The degree of substitution and Mw of the amphiphilic HA controls the sterilization by filtration. The protection against desiccation was tested using human keratinocytes (HaCaT) cells lines., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We determined the effects of biochar on starch properties and the activities of enzymes and expression levels of genes related to starch in two Japonica rice cultivars. The two rice varieties were subjected to five biochar treatments (0, control; and 5, 10, 20, and 40 t/hm 2 ). In both rice varieties, the content of apparent amylose and resistant starch were lower in biochar treatments than in the control. The proportion of fa chains was higher and that of fb3 chain was lower in the biochar treatments than in the control. Starch viscosity and cooking taste quality were improved by the biochar treatments. In both rice varieties, the activity of granule-bound starch synthase was significantly decreased by biochar treatments, and the activities of soluble starch synthase, starch branching enzyme, and starch debranching enzyme were significantly increased. The transcript levels of genes encoding starch synthases and starch branching enzymes were significantly increased by biochar treatments. We conclude that biochar at a dose of 5-10 t/hm 2 can regulate the activity of starch-related enzymes, and this affects the type, content, and fine structure of starch. Therefore, the addition of biochar to soil can improve the viscosity and taste quality of rice starch.

Uncontrolled hemorrhage is a large cause of death in the global scope, thus leading to an urgent demand to develop efficient hemostatic materials. In this study, a series of modified cotton fabrics (MCFs) with different carboxymethyl group contents were prepared from cotton fabric (CF) by a carboxymethylation process to choose the appropriate one with the best hemostatic performance. The carboxymethyl group contents of MCFs rose up as the dosages of ClCH 2 COOH increased. The crystallinity of CF decreased after carboxymethylation, and MCFs can dissolve slightly with the phenomenon that there were vague boundaries between fibers after being treated with water. Furthermore, the MCF with the carboxymethyl group content at 0.77 mmol/g (MCF-0.77) could absorb the blood quickly, achieve dense distribution of blood cells and have high viscosity of leaching liquor. In addition, the MCF-0.77 with good biocompatibility accelerated the hemostasis time to 46.6 ± 8.4 s compared with the CF (88.8 ± 31.5 s) in a rat model of liver injury. In summary, the prepared MCF-0.77 is a potential hemostatic wound dressing for clinical use since every second counts for pre-hospital care., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A facility for performing serial crystallography measurements has been developed at the Australian synchrotron. This facility incorporates a purpose built high viscous injector, Lipidico, as part of the macromolecular crystallography (MX2) beamline to measure large numbers of small crystals at room temperature. The goal of this technique is to enable crystals to be grown/transferred to glass syringes to be used directly in the injector for serial crystallography data collection. The advantages of this injector include the ability to respond rapidly to changes in the flow rate without interruption of the stream. Several limitations for this high viscosity injector (HVI) exist which include a restriction on the allowed sample viscosities to >10 Pa.s. Stream stability can also potentially be an issue depending on the specific properties of the sample. A detailed protocol for how to set up samples and operate the injector for serial crystallography measurements at the Australian synchrotron is presented here. The method demonstrates preparation of the sample, including the transfer of lysozyme crystals into a high viscous media (silicone grease), and the operation of the injector for data collection at MX2.

Preferential interactions of formulation excipients govern their impact on the stability properties of proteins in solution. The ability to predict these interactions without the need to perform experiments would enable formulation design to begin early in the development of a new antibody therapeutic. With that in mind, we developed a feature set to numerically describe local regions of an antibody's surface for use in machine learning applications. Then, we used these features to train machine learning models for local antibody-excipient preferential interactions for the excipients sorbitol, sucrose, trehalose, proline, arginine·HCl, and NaCl. Our models had accuracies of up to about 85%. We also used linear (elastic net) models to quantify the contribution of antibody surface features to the preferential interaction coefficients, finding that the carbohydrates and proline tend to have similar important features, while the interactions of arginine·HCl and NaCl are governed by charge features. We present several case studies demonstrating how these machine learning models could be used to predict experimental aggregation and viscosity behavior in solution. Finally, we propose an approach to computational formulation design wherein a panel of excipients may be considered while designing an antibody sequence.

The aim of this in vitro study was to evaluate the effect of bleaching protocols on the surface roughness (Ra), color change and surface micromorphology of a low-viscosity bulk-fill composite (Filtek Bulk Fill Flow, 3M ESPE), a highviscosity bulk-fill composite (Filtek Bulk Fill, 3M ESPE) and a conventional nanoparticulate composite resin (control) (Filtek Z350 XT, 3M ESPE). Forty samples of each composite (disks 5 mm in diameter and 2 mm thick) were randomly divided into four groups (n=10), according to bleaching protocol: a) 10% carbamide peroxide gel (Opalescence, Ultradent Products) (2 h/ day, for 14 days); b) 40% hydrogen peroxide gel (Opalescence Boost, Ultradent Products) (three bleaching sessions, once a week, 45 min/session); c) whitening rinse (Listerine Whitening Extreme, Johnson & Johnson) (2 min/day, for 14 days); and d) distilled water (control). The samples were submitted to triplicate readings (Ra and color [CIELAB parameters]) before and after contact with bleaching protocols. Micromorphology was analyzed in a scanning electron microscope (SEM). Ra and color parameters (ΔL, Δa, Δb and ΔE) were analyzed by generalized linear models (α=0.05). The Ra of the high-viscosity bulk-fill was significantly higher than that of the other composites (p<0.05). Ra increased significantly (p<0.05) and surface became more irregular (SEM analysis) in all the composite resins, regardless of the bleaching protocol (p<0.05). The high-viscosity bulk-fill composite resin group had significantly lower ΔE (p<0.05) than the nanoparticulate composite resin group immersed in distilled water. It was concluded that the characteristics of each resin significantly influenced the Ra more than the bleaching protocol. The high-viscosity bulk-fill resin presented minor color change., Competing Interests: none, (Sociedad Argentina de Investigación Odontológica.)

Objectives: The aim of the study was to determine the quantitative and qualitative surface structure of contemporary RBCs in posterior teeth reconstructions: regular viscosity bulk fill and conventional composites, obtained after two-stage polishing procedure., Materials and Methods: Four conventional nanohybrid composites (Tetric EvoCeram, GrandioSO, Filtek Z550, and Ceram·X Mono) and four regular viscosity bulk fill composites (Tetric EvoCeram Bulk Fill, X-tra fil, Filtek Bulk Fill Posterior, and QuixFil) were tested. Samples of each RBC were prepared using PMMA cylindrical mold. After two-step polishing procedure, a surface geometry was evaluated under profilometry (Turbowave v. 7.36, Hommel-Etamic) and SEM (VEGA 3, Tescan Analytics). To evaluate differences between values, the following nonparametric tests were used: Friedman's ANOVA, Wilcoxon's matched-pair test, ANOVA Kruskal-Wallis, and Mann-Whitney U ., Results: All conventional RBCs showed Ra values in the range of 0.20-0.26  μ m. Bulk fill showed higher values in range of 0.49-1.36  μ m except for Filtek Bulk Fill Posterior, which achieved 0.23  μ m Ra value. SEM images of conventional RBCs were described as smooth surfaces with slight damage except for TEC, which presented smooth surface with no damage. Bulk fill composites showed rough surface, except for TBF, which presented smooth surface with slight damage., Conclusions: Regular viscosity bulk fill composites do not constitute a homogeneous group regarding surface roughness after polishing. They obtain, for the most part, poorer smoothness values after polishing than conventional RBCs., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Mateusz Granat et al.)

Purpose: To determine the effect of particle size and viscosity of suspensions on topical ocular bioavailability of budesonide, a corticosteroid drug. Methods: Budesonide microparticle and nanoparticle (MP and NP) suspensions were prepared with or without homogenization and microfluidization. Using different grades of hydroxyl propyl methyl cellulose, low viscosity NP (NP-LV) and low and high viscosity MP (MP-LV and MP-HV) were prepared. Suspensions were characterized for particle size, viscosity, and osmolality. Budesonide suspensions were administered topically to rabbits and aqueous humor was collected and analyzed for budesonide. Budesonide C max , t max , and the area under the concentration time curve (AUC (0-6h) ) values were determined. The geometric mean ratio of AUC and bioequivalence was evaluated using a bootstrap method. Results: The particle sizes for NP and MP were ∼700 and 2,000 nm. The viscosities for low and HV formulations were ∼5 and 50 cP. The geometric mean budesonide C max values for the suspensions NP-LV, MP-LV, and MP-HV were 0.22, 0.22, and 0.31 μg/g, t max values were 0.67, 0.60 and 0.53 h, and AUC 0-6h values were 0.72, 0.53, and 0.95 μg h/g, respectively. Bootstrap analysis indicated that the 90% confidence intervals of the geometric mean ratio of AUC 0-6h values were 1.00-1.74 (MP-HV vs. NP-LV), 0.57-0.96 (MP-LV vs. NP-LV), and 0.45-0.70 (MP-LV vs. MP-HV). Conclusions: The 3 budesonide suspensions assessed in this study were not bioequivalent. Results suggested that an increase in viscosity improves the bioavailability of budesonide from the microsuspension formulation.

The rheological, prebiotic, and anti-inflammatory properties of neutral polysaccharide extracted from maca roots (MP) were investigated. MP was composed of arabinose, galactose, rhamnose, and glucose. In steady shear rheological properties, an increasing concentration of MP solution exhibited higher apparent viscosity (η a,100 ) and consistency index (K) under acidic condition (pH 4). In dynamic rheological properties, the dynamic moduli (G' and G″) in the frequency sweep test from the MP solution were increased with increasing concentration and decreasing pH. The changes in dynamic moduli of the MP solution with various concentrations and pH values were stable during 1 h storage at 4 °C due to the enhancement of hydrogen bonding. According to the results of the temperature sweep test, an increasing concentration of MP solution increased dynamic moduli under acidic conditions. The prebiotic properties of MP induced a higher growth of Bifidobacterium longum ATCC15707 and Lactobacillus rhamnosus ATCC 7469 than inulin and increased acetic acid, propionic acid, and butyric acid more than inulin in vitro. Furthermore, MP inhibited lipopolysaccharide-induced NO production in RAW 264.7 cells, which indicated that an increasing concentration of MP enhanced anti-inflammatory activities. Therefore, MP is a potential functional material for the food and pharmaceutical industries., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

We utilized the reaction of chitosan with acetic anhydride to form a chitin gel. This gel was then dried, which formed a chitin sheet. The procedure was extremely easy for a biologist unfamiliar with materials engineering. Spheroids derived from HEK293T cells were formed on the chitin sheet, because the spheroids slightly attached and slowly moved on the chitin sheet.

The goal of this work was to study the characteristics of a new phospholipid nanovesicular carrier for nasal administration of drugs. Multilamellar vesicles were visualized by electron microscopy, and their mean distribution size of 200 nm was evaluated by DLS. Measured pH and viscosity values were found adequate for a nasal delivery carrier. CLS micrographs of the nasal mucosa of rats following administration of the carrier incorporating probes with various properties show delivery into the nasal mucosa layers. Tramadol containing systems were characterized and tested for their analgesic effect in two pain animal models. In mice, a significantly higher antinociceptive effect and a rapid onset of action were obtained as compared to other nasal delivery carriers and to oral treatment. This enhanced analgesic effect was further confirmed in rat pain model and sustained by drug plasma and brain levels. To test the systems behavior in a larger animal, a pharmacokinetic crossover study was carried out in sheep after administrating Tramadol nasally in the nanocarrier and IV. The plasma and CSF absolute bioavailability values were 1.09 and 0.87, respectively. HPLC and LC-MS/MS methods for quantification of Tramadol in plasma, brain and CSF were developed and are presented here. It is noteworthy that no pathological alterations or inflammation signs were observed in rat nasal mucosa following sub-chronic treatment. The results obtained in this work encourage further investigation of using the new carrier for nasal delivery of drugs in humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The current first line therapy for oral mucositis pain control is unsatisfactory as it results in only a short duration of modest pain relief. Developing mucoadhesive in situ forming formulations to prolong pain relief is challenging due to their complex physicochemical properties and the unique requirements for oral mucosa application. The objective of this study is to develop a mucoadhesive in situ forming gel to deliver a novel drug molecule, Bupivacaine γ-linoleate (Bup-γL), for prolonged and more potent oral mucositis pain control. The formulation is sprayable at room temperature, and forms a mucoadhesive gel on contact with the oral mucosa. The pain would be managed by forming an adhesive protective layer from irritating agents (such as bacteria, food, etc.), and also by anesthetizing the nerve cells with Bup-γL. Pluronic® F127 and F68 were used to achieve in situ forming properties. Either Carbopol® or Noveon® was included as a mucoadhesion enhancer. Formulation preparation methods were extensively investigated. The physicochemical properties of the gels were characterized, including gelation behavior, ex vivo mucoadhesion, rheological properties, in vitro drug release and sprayability. The polymer mixing sequence was determined to have a profound impact on the preparation time of blank formulations. A final drug content in a range of 6.21-6.51 mg/mL was obtained using the optimized method. The gelation temperature was significantly reduced by the addition of hydrophobic Bup-γL. Both Carbopol® and Noveon® significantly improved mucoadhesion without compromising the other main properties of the system (such as gelation temperature and drug content). Drug release from the formulation showed pH sensitive responses where lower pH favored faster drug release due to the ionization of Bup-γL. This study offers a promising strategy to achieve prolonged oral mucositis pain control. Moreover, a promising platform for the mucoadhesive in situ gels that allows high loading of hydrophobic drugs has been developed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Virgibacillus salarius BM02 was identified as a highly exopolysaccharide (EPS) producing bacterium. The EPS production and its physico-chemical properties (intrinsic viscosity and total sugars/protein (TS/P) ratio) were optimized using Box-Behnken experimental design. Maximum EPS production of 5.87 g L -1 with TS/P ratio of 12.56 and intrinsic viscosity of 0.13 dL g -1 was obtained at optimal conditions of sucrose (4.0% w/v), peptone (0.75% w/v) and incubation period of 4.69 day. The monosaccharide composition of EPS was mannose, arabinose and glucose at a molar ratio of 1.0:0.26:0.08. The EPS showed high water solubility (38.5%), water holding capacity (514.46%) and foaming capacity (55.55%). The EPS showed moderate antioxidant activity in vitro and good emulsion stabilizing properties against several hydrophobic compounds. The emulsifying activity was stable at different temperatures, pH and ionic strength. Additionally, the acid hydrolysate of the EPS was evaluated as a carbon source for the mixotrophic cultivation of industrially important Spirulina platensis. It induced an enhancement of not only biomass production of S. platensis, but also cellular contents (pigments, proteins and lipids) leading to higher nutritional value., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Inspired by mucus, which provides an ideal supramolecular model and whose fluid-like (viscous) and solid-like (elastic) behaviors can be adjusted to meet different physiological requirements, we report oil-regulated supramolecular adhesives by the co-assembly of polyurea oligomers and carvacrol oils. The adhesive is crosslinked by weak but abundant hydrogen bonds, which can be regulated by the incorporated carvacrol oils through the competition of intermolecular hydrogen bonds, presenting a unique set of mucus-mimicking features including oil-regulated mechanics, processability, reusable adhesivity, and extreme longevity in both air and water. Owing to the intrinsic bactericidal effect of the carvacrol oils, the developed adhesives can serve as potent antibacterial coatings with both rapid contact killing (99.9% killing within 15 min) and long-term controlled release abilities (up to 70 days), enabling versatile antibacterial applications in diverse conditions. We envision that these adhesives will be useful in buildings and architectures, community and public facilities, food storage and packaging technologies, functional textiles, and practical biomedical fields.

Viscoelastic blends of biodegradable polyesters with low and high molecular weight distributions have remarkably strong adhesion (significantly greater than 1 N/cm 2 ) to soft, wet tissue. Those that transition from viscous flow to elastic, solidlike behavior at approximately 1 Hz demonstrate pressure-sensitivity yet also have sufficient elasticity for durable bonding to soft, wet tissue. The pressure-sensitive tissue adhesive (PSTA) blends produce increasingly stronger pull-apart adhesion in response to compressive pressure application, from 10 to 300 s. By incorporating a stiffer high molecular weight component, the PSTA exhibits dramatically improved burst pressure (greater than 100 kPa) when used as a tissue sealant. The PSTA's biodegradation mechanism can be switched from erosion (occurring primarily over the first 10 days) to bulk chemical degradation (and minimal erosion) depending on the chemistry of the high molecular weight component. Interestingly, fibrosis toward the PSTA is reduced when fast-occurring erosion is the dominant biodegradation mechanism.

Recent studies show that understanding the rheological properties of thickened fluids, such as viscosity and yield stress, is advantageous in designing optimal thickened fluids for the treatment of dysphagia. To date, these studies have focused on the rheological behavior of thickened fluids in shear deformation, while limited information is available on the surface tension of thickened fluids or their rheological behavior in extensional deformation. Knowledge of the extensional properties of thickened fluids (extensional viscosity and cohesiveness) is important to fully understand the behavior of such fluids while swallowing. Our aim in this work, therefore, was to characterize water and skim milk thickened with a commercial thickener (xanthan gum based) to determine extensional deformation and surface tension properties. It was observed that the surface tension decreases as the thickener concentration increases due to the accumulation of the biopolymer at the surface of the fluid when it dissolves in water. In addition, the extensional viscosity of the fluid increased over time as the filament thinned (i.e., as the Hencky strain increased) until it reached a plateau. It was observed that the maximum extensional viscosity, which is related to the cohesiveness of the fluid, increases with the higher concentrations of thickener. However, the cohesiveness of thickened skim milk was lower than that of the thickened water at a given thickener concentration due to lower surface tension. This study confirms that by increasing the concentration of thickener, it will not only increase the shear viscosity (i.e., bolus thickness) of the fluid, but also the extensional viscosity (i.e., bolus cohesiveness).

Background: All over the world, people face the same skin problems. However, their skin characteristics are different. Thus, it is a challenge to prescribe treatments that will be effective on different skin types. Therefore, it is very important to consider the skin biology when indicating a dermocosmetic treatment., Objectives: To assess skin biophysical parameters in French and Brazilian subjects and to verify the efficacy of four dermocosmetic treatments in these populations., Methods: Five test areas were defined on each volar forearm of the eighteen Brazilian and eighteen French participants using a randomized design. Biophysical measurements in terms of skin hydration, skin barrier function, skin brightness, and skin viscoelasticity were performed before and after 60 minutes of treatment., Results: Skin biophysical differences between populations were found. French skin has been shown to be more hydrated regarding epidermal mechanic properties and stratum corneum water content and more radiant when compared with Brazilian skin. However, it showed more signs of cutaneous aging and fatigue effects on skin. The Brazilian skin showed better skin barrier function. In addition, the treatments were effective in both populations., Conclusions: Despite the differences found in French and Brazilian skin, the proposed dermocosmetic treatments showed effective in both populations., (© 2019 Wiley Periodicals, Inc.)

Objective: Aim of the present work was to optimize and formulate resveratrol loaded vesicular cream intended for dermal delivery of resveratrol with high skin deposition potential. Methods: Formulation was developed and optimized using Central Composite Design. Amount of phospholipid and sodium cholate were selected as critical material attributes and vesicle size and entrapment efficiency of resveratrol were taken as critical quality attributes. To increase the skin applicability and patient compliance, vesicles were further developed as vesicular cream which was then thoroughly characterized for physicochemical parameters, ex vivo skin permeation/deposition profile and antioxidant potential. Results: Vesicle size and entrapment efficiency of the optimized batch were found to be 178.9 ± 12.87 nm with 72.32 ± 3.45% respectively. Physicochemical properties and viscosity of cream formulation were also found to be favorable for skin applicability. Permeation flux at the end of 24 h was found to be 2.70 ± 0.73, 4.45 ± 0.56 and 4.95 ± 0.69 µg cm -2 h -1 for conventional cream, vesicular dispersion, and vesicular cream formulation respectively. Higher drug deposition in the skin via vesicular cream formulation was observed i.e. 335.2 ± 4.12 µg cm -2 (70.16 ± 0.87%) as compared to conventional cream i.e. 67.12 ± 19.63 µg cm -2 (14.05 ± 4.11%). Resveratrol encapsulated in vesicular cream has retained its inherent antioxidant activity suggesting the stability of resveratrol in vesicular cream. Conclusion: Thus, it can be concluded that deformable vesicular cream is capable of delivering encapsulated bioactive in deeper layers of skin, where it can be retained for achieving higher dermatological benefits.

Objective: The aim of this study was to develop an emulgel for the treatment of rosacea, applying quality by design (QbD). Methods: An emulgel designed to release the active pharmaceutical ingredients (APIs), metronidazole and niacinamide, via an emollient formulation that favors residence time and attenuates facial redness would be an excellent vehicle to develop to treat rosacea. It was decided to design first a vehicle presenting the attributes established in the quality target product profile, and then, after selecting the best formulation, to load the APIs in it to optimize the final emulgel. A design of experiments was introduced to study the effect of formulation variables on quality attributes (adhesion, phase separation by mechanical stress and viscosity) of the emulgels. Response surface methodology and desirability functions were applied for data analysis. After optimization, the final emulgel was further characterized by assay and in vitro release of APIs, attenuation of facial redness, and compared to commercially available metronidazole products regarding API release. Results: The final emulgel gradually released both APIs, reaching approximately 88% within the first 4 h, and their profiles were well described by the Higuchi model. Only a light attenuation effect to conceal facial redness was achieved. Conclusions: A metronidazole and niacinamide emulgel, also providing cosmetic assistance, was developed using QbD. The emulgel releases metronidazole faster than the creams, but more gradually than the commercially available gel, providing a realistic time frame of drug delivery in accordance with the expected time of residence of the adhesive emulgel over the affected facial area.

Hyperviscosity agents are commonly used in ophthalmic formulations for improving corneal drug penetration by increasing tissue contact time. One such viscosity agent is hydroxypropyl methylcellulose (HPMC). HPMC has been used in riboflavin solutions for photochemical UVA cross-linking (CXL). Sodium hydroxymethylglycinate (SMG) is a small molecule formaldehyde releaser that can function as a therapeutic tissue cross-linker for corneal and scleral applications. The present study was undertaken in order to study formulation factors using HPMC and SMG that could positively influence the cross-linking effect in these ocular tissues. Formulations containing 10 mM SMG and 100 mM sodium bicarbonate were prepared with varying HPMC concentrations from 0 to 4.4%. Their cross-linking effects on porcine and rabbit eyes were measured using differential scanning calorimetry (DSC), expressed as the change/difference in melting temperature (ΔTm) compared with the control. SMG in 4.4% HPMC solution resulted in ΔTm of 6.3 ± 1.21, while other concentration showed no differences in Tm shift on porcine cornea. In ex vivo rabbit cornea, there was a trend toward an increasing cross-linking effect with higher viscosity albeit mild differences. While a significant Tm shift was observed in porcine and rabbit sclera, there was no difference in effect of cross-linking between four HPMC concentrations. Increasing the HPMC concentration does not negatively affect the cross-linking efficacy attributed by SMG and could still be a positive cross-linking enhancer by virtue of increasing tissue contact time in a dynamic biological system. This information will be useful for planning further animal and human studies., (© 2020 The Author(s).)

The purpose of this study was to evaluate the effect of plasticizer type (glycerol, PEG-400, and sorbitol) and concentration (0%, 15%, 30% and 45%, w/w dry polymer weight) on rheological and physico-mechanical and structural properties of chitosan/zein blend film. Based on the analysis of rheological properties of chitosan/zein film-forming solutions, all film-forming solutions exhibited non-Newtonian behavior. The flow index of film-forming solution increased and apparent viscosity decreased with the increase of plasticizer concentration. The storage modulus (G') and the loss modulus (G″) decreased when plasticizer was added. The permeability of films increased significantly with the increase of plasticizer concentration, but the C/Z-P film (plasticized chitosan/zein film with PEG-400) had better barrier performance compared with the other two. The C/Z-P film had better mechanical properties and light transmission. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) revealed chitosan and zein had good compatibility due to the addition of the plasticizer, and crystallinity decreased with the increase of plasticizer concentration., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study aimed to prepare and characterize organogels containing microparticles of ascorbic acid (AA) obtained from propolis by-product. The formulations F1 (5% of microparticles) and F2 (10% of microparticles) were evaluated regarding rheological and textural properties, antioxidant and radical scavenging activity, in vitro release and cellular studies. The organogels showed plastic flow behavior and rheopexy. The textural parameters were within acceptable values for semisolid formulations. The antioxidant capacity of organogels F1 and F2 by the DPPH assay demonstrated IC 50 ranging from 1523.59 to 1166.97 μg/mL, respectively. For the FRAP assay, the values found were 842.88 and 956.14 μmol of FSE/g formulation, respectively. Good scavenging activity against nitrogen species was observed. The concentration of 63 μg/mL did not present toxicity on HaCaT and HFF-1 cells. In vitro release profile of AA from organogels showed a slow pattern of drug release, mainly for F2. Therefore, the proposed organogel containing AA microparticles with propolis by-product matrix represents a promising platform for topical drug delivery with antioxidant effect.

Polyphenols are secondary plant metabolites, which have received much attention because of their potential health benefits. Silibinin (SIL) is a well-known naturally occurring flavonolignan, which is extensively used in treating a wide variety of diseases as a dietary supplement as well as a prescribed drug. The mechanism of binding of SIL to calf thymus DNA (ctDNA) was investigated by employing multispectroscopic techniques, viz., absorption, fluorescence, and circular dichroism besides viscosity measurements and docking studies. Analysis of fluorescence results indicated that SIL has interacted with ctDNA and quenched its intensity through static quenching mechanism. The binding constant at room temperature was found to be 2.48×10 4 mol -1 , suggesting moderate binding affinity between SIL and ctDNA. The hypochromicity observed in the absorption spectra of ctDNA in the presence of SIL revealed the intercalation of SIL into ctDNA base pairs. Further, the intercalative mode of binding between SIL and ctDNA was confirmed by viscosity measurements and molecular docking studies. The outcome of present study helps to decipher the interaction mechanism between SIL and DNA at physiological pH, which further assists in the design of a new analogue for better therapeutic effects., (© 2019 John Wiley & Sons, Ltd.)

Background: The combination of oral supplementation and topical formulations to the improvement of skin conditions has been proposed as an innovative approach to obtain effective treatments. However, studies comparing the effectiveness of each type of treatments are still in lack. This way, the objective of this work was to evaluate the clinical efficacy of a dermocosmetic formulation with di- and tripeptides, as well the effects of an oral supplementation based on hydrolyzed collagen through biophysical and skin imaging techniques., Methods: Sixty healthy female subjects, aged between 40 and 50 years, were enrolled, being separated in 3 groups: topical formulation, oral supplementation, and oral placebo. The stratum corneum water content, skin viscoelasticity, dermis echogenicity, and skin pores parameters were evaluated., Results: The group with the topical formulation showed a significant increase in the stratum corneum water content and skin elasticity after 28-day period and also acted in the dermis echogenicity after 90 days with the formulation with peptides. The oral supplementation acted on skin elasticity and presented a more pronounced effect on dermis echogenicity, reducing skin pores after 90-day period., Conclusion: The obtained results with oral supplementation and topical application of hydrolyzed proteins were considered complementary in the improvement of general skin conditions, acting in different mechanisms., (© 2019 Wiley Periodicals, Inc.)

Although efficient and inexpensive, conventional viscometry to determine the average degree of polymerization (DP) of cellulose may mislead the final DP because cellulose degradation occurs in the used solvents, which consist of alkaline amino complexes of transition metals, such as cupri-ethylenediamine (CED). For oxidatively damaged pulps or celluloses, viscosity-DP determinations may be more inaccurate because alkali-induced β-elimination reactions render such oxidized celluloses even more vulnerable. Despite the risk identified in many studies, a systematic investigation of the parameters affecting the viscosity-DP assessed by reliable analytics is still required. Here, a new approach evaluating the effects of CED on oxidized cellulosics was used (i.e., immediate pulp regeneration after dissolution in CED). In-depth molecular feature characterization (e.g., absolute molar masses and oxidized groups' profiling related to molecular weight distribution) by gel permeation chromatography coupled with fluorescence and multiangle laser light scattering clarified the behavior of oxidized celluloses and the influencing parameters upon dissolution in CED.

Nanoviscosity of the cytoplasm is a key factor affecting diffusion of biomolecules and - as a consequence - rates of biochemical reactions in a cell. Nanoviscosity is an outcome of variable chemical and structural factors, which can temporarily change with cell-cycle associated changes of intracellular architecture. Thus, the question arises, whether rates of biochemical reactions depend on the point of cell cycle. In this paper we address this topic by constant observation of nanoviscosity of HeLa cells cytoplasm during S, G2 and G1 phases after Aphidicolin synchronization. For this purpose we measured diffusion rates of EGFP molecules using fluorescence correlation spectroscopy (FCS). To our surprise, a counter-intuitive stability of cytoplasmic viscosity was observed during the cell cycle. Our results hint at possible existence of robust mechanism maintaining stable physiological viscosity of the cytoplasm, despite huge structural changes during cell cycle.

Under pathological conditions, the joint is not well lubricated, which inevitably leads to osteoarthritis. Currently, in clinics injection of hyaluronic acid (HA) as an intra-articular viscosupplement is one of the main methods for alleviation of osteoarthritis. However, the viscosity of HA reduces dramatically under high shear rate due to the shear-thinning effect. Therefore, it is crucial to enhance the lubrication property of HA in order to treat osteoarthritis effectively. In this study, we successfully grafted 2-methacryloyloxyethyl phosphorylcholine (MPC), which is a zwitterionic biomaterial with excellent hydration lubrication, onto the HA with two different molecular weights (HAMPC) to enhance lubrication. The lubrication test performed using an atomic force microscope showed that, compared with HA, the friction coefficient of HAMPC was greatly reduced under various conditions. The in vitro test demonstrated that HAMPC was biocompatible and could upregulate cartilage anabolic genes while simultaneously downregulating cartilage catabolic proteases and pain-related genes. Importantly, high molecular weight HAMPC exhibited improved the capability to regulate these genes compared with low molecular weight HAMPC. In conclusion, the high molecular weight HAMPC developed herein, with enhanced lubrication and anti-inflammation, may be a promising polymer for the treatment of osteoarthritis.

Viscoelasticity has emerged as a critical regulator of cell behavior. However, there is an unmet need to develop biomaterials where viscoelasticity can be spatiotemporally controlled to mimic the dynamic and heterogeneous nature of tissue microenvironments. Toward this objective, we developed a modular hyaluronic acid hydrogel combining light-mediated covalent and supramolecular cross-linking to afford spatiotemporal control of network viscoelastic properties. Covalently cross-linked elastic hydrogels or viscoelastic hydrogels combining covalent and supramolecular interactions were fabricated to match healthy and fibrotic liver mechanics. LX-2 human hepatic stellate cells cultured on viscoelastic hydrogels displayed reductions in spreading, actin stress fiber organization, and myocardin-related transcription factor A (MRTF-A) nuclear localization compared to cells on elastic hydrogels. We further demonstrated the dynamic capabilities of our hydrogel system through photo-mediated secondary incorporation of either covalent or supramolecular cross-links to modulate viscoelastic properties. We used photopatterning to create hydrogels with well-controlled patterned regions of stiff elastic mechanics representing fibrotic tissue nodules surrounded by regions of soft viscoelastic hydrogel mimicking healthy tissue. Cells responded to the local mechanics of the patterned substrates with increased spreading in fibrosis-mimicking regions. Together, this work represents an important step forward toward the creation of hydrogel models with spatiotemporal control of both stiffness and viscoelastic cell-instructive cues.

Electrospun biopolyelectrolyte nanofibers hold potential for use in a range of biomedical applications, but eliminating toxic chemicals involved in their production remains a key challenge. In this study, we successfully electrospun nanofibers from an aqueous complex coacervate solution composed of chitosan and hyaluronic acid. Experimentally, we investigated the effect of added salt and electrospinning apparatus parameters, such as how applied voltage affected fiber formation. We also studied how the addition of alcohol cosolvents affected the properties of the coacervate solution and the resulting nanofibers. Overall, we observed a trade-off in how the addition of salt and alcohol affected the phase behavior and rheology of the coacervates and, consequently, the size of the resulting fibers. While salt served to weaken electrostatic associations within the coacervate and decrease the precursor solution viscosity, the addition of alcohol lowered the dielectric constant of the system and strengthened these interactions. We hypothesize that the optimized concentration of alcohol accelerated the solvent evaporation during the electrospinning process to yield desirable nanofiber morphology. The smallest average nanofiber diameter was determined to be 115 ± 30 nm when coacervate samples were electrospun using an aqueous solvent containing 3 wt % ethanol and an applied voltage of 24 kV. These results demonstrate a potentially scalable strategy to manufacture electrospun nanofibers from biopolymer complex coacervates that eliminate the need for toxic solvents and could enable the use of these materials across a range of biomedical applications.

Research on pharmaceutical pediatric powder-for-suspension formulations mainly focuses on chemical and physical stability of the active pharmaceutical ingredient. However, the chemical stability of excipients could also play a key role in governing the quality and performance of the product. The suspending agents that are added into formulations to suspend the active pharmaceutical ingredient particles are critical to ensure the suspension dose accuracy. In this article, we investigate the chemical stability of the suspending agent-xanthan gum-in the presence of other excipients, particularly commonly used acid modifiers (i.e., citric acid, malic acid, succinic acid, and fumaric acid) in pediatric powder-for-suspension formulations. We observed that some of the acid modifiers catalyze cross-linking of xanthan gum during accelerated stability studies in powder blends, which significantly decreases the viscosity of the corresponding constituted suspension, resulting in poor suspendability and dose inaccuracy. Furthermore, we found that the cross-linking of xanthan gum is acid-dependent and that a careful selection of acid modifiers can mitigate the degradation issues of xanthan gum. Finally, we characterized the cross-linked xanthan gum using Fourier transform infrared spectroscopy and solid-state nuclear magnetic resonance and discussed the possible degradation mechanisms., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to develop an ibuprofen microemulsion (IBU-ME) incorporated into in situ gels (microgels) for local delivery into periodontal pockets. The IBU-ME was prepared at a concentration of 1% w/v IBU. Various concentrations of the thermosensitive Pluronic® F127 (P127) solution and a series of combinations of the P127 solution and IBU-ME at a 1:1 ratio were initially developed and tested to determine their sol-gel transition temperatures (T sol→gel ). Based on these studies, a constant concentration of P127 (11.1% w/v) and variable concentrations of IBU-ME were used to prepare the microgels. The mechanical properties (T sol→gel , gelling time (T gel ), viscosity, and viscoelastic properties) of the microgels were evaluated. The release of IBU from the microgels was determined in vitro. Rheological stability studies were performed to investigate the mechanical properties of the microgels after one month. The transition behavior studies demonstrated that the microgels are thermosensitive systems with pseudoplastic flow and their viscoelastic properties indicated that the elastic property was greater than the viscous property (G' > G″). The results showed that the mechanical properties of the microgels depend on the concentration of IBU-ME. In addition, rheological stability studies demonstrated that T gel and T sol→gel are increased after one month, whereas the viscosity and viscoelastic properties are decreased after one month. Owing to the rigid structure of the microgels, the release of IBU from the microgels followed a controlled-release pattern., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent experiments show that synthetic polymers can influence the degree of microbial aggregation and the rheological properties of bacterial suspensions, the study of which can help us control biofilm formation. In this article, we add polyethylene glycol (PEG) with various molecular weights and concentrations into two types Bacillus subtilis cell cultures, Luria Broth (LB) and Minimal Salts glutamate glycerol (MSgg), respectively. We first observe cell clusters in cell suspensions with various concentrations of PEG, and measure cluster size in both static and dynamic fluid environments. We find that cells gather together into big clusters and most of the cells are arranged longitudinally; and the large cell clusters are divided into smaller aggregates under fluid shear. We then use a rheometer to measure the viscoelastic properties of various cell cultures, to represent the degree of aggregation of the bacterial suspensions. We find the storage modulus, the loss modulus and the viscosity of bacterial suspensions not only depend on the cell aggregation but also depend on the directionality of cellular motion.

Chemicals capable of producing structural and chemical changes on cells are used to treat diseases (e.g., cancer). Further development and optimization of chemotherapies require thorough knowledge of the effect of the chemical on the cellular structure and dynamics. This involves studying, in a noninvasive way, the properties of individual cells after drug administration. Intracellular viscosity is affected by chemical treatments and it can be reliably used to monitor chemotherapies at the cellular level. Here, cancer cell monitoring during chemotherapeutic treatments is demonstrated using intracellular allocated upconverting nanorockers. A simple analysis of the polarized visible emission of a single particle provides a real-time readout of its rocking dynamics that are directly correlated to the cytoplasmic viscosity. Numerical simulations and immunodetection are used to correlate the measured intracellular viscosity alterations to the changes produced in the cytoskeleton of cancer cells by anticancer drugs (colchicine and Taxol). This study evidences the possibility of monitoring cellular properties under an external chemical stimulus for the study and development of new treatments. Moreover, it provides the biomedical community with new tools to study intracellular dynamics and cell functioning., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)