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  • Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, and , were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both and and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues.

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  • The purpose of this work was to evaluate the possibility of adding tea saponin (TS) to reduce the synthetic surfactant concentration, and maintain or improve the shelf stability of nanoemulsions. The essential oil (2.5 wt%) loaded oil-in-water nanoemulsions were co-stabilized by Tween 40 (0.5-2.5 wt%) and TS (0.1-5 wt%). A combination of several analytical techniques, such as dynamic laser scattering, interfacial tension, zeta potential, and transmission electron microscope, were used for the characterization of nanoemulsions. Low levels of TS (0.1-0.5 wt%) with Tween 40 had significant effects on the emulsification, and a nanoemulsion with the smallest droplet diameter of 89.63 ± 0.67 nm was obtained. However, in the presence of high TS concentration (0.5-5 wt%), micelles generated by the non-adsorbed surfactants in the aqueous lead to droplets growth. In addition, the combinations of Tween 40 and TS at the high level (>3.5 wt%) exerted a synergistic effect on stabilizing the nanoemulsions and preventing both Ostwald ripening and coalescence. The negative charged TS endowed the droplets with electrostatic repulsion and steric hinderance appeared to prevent flocculation and coalescence. These results would provide a potential application of natural TS in the preparation and stabilization of nanoemulsions containing essential oil.

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  • Growing evidence has shown that some pharmaceutical excipients can act on drug transporters. The present study was aimed at investigating the effects of 13 commonly used excipients on the intestinal absorption of metformin (MTF) and the underlying mechanisms using Caco-2 cells and an mouse non-everted gut sac model. First, the uptake of MTF in Caco-2 cells was markedly inhibited by nonionic excipients including Solutol HS 15, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, and crospovidone. Second, transport profile studies showed that MTF was taken up via multiple cation-selective transporters, among which a novel pyrilamine-sensitive proton-coupled organic cation (H/OC) antiporter played a key role. Third, Solutol HS 15, polysorbate 40, and polysorbate 60 showed -inhibitory effects on the uptake of either pyrilamine (prototypical substrate of the pyrilamine-sensitive H/OC antiporter) or 1-methyl-4-phenylpyridinium (substrate of traditional cation-selective transporters including OCTs, MATEs, PMAT, SERT, and THTR-2), indicating that their suppression on MTF uptake is due to the synergistic inhibition toward multiple influx transporters. Finally, the pH-dependent mouse intestinal absorption of MTF was significantly decreased by Solutol HS 15, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, and pyrilamine. In conclusion, this study revealed that a novel transport process mediated by the pyrilamine-sensitive H/OC antiporter contributes to the intestinal absorption of MTF in conjunction with the traditional cation-selective transporters. Mechanistic understanding of the interaction of excipients with cation-selective transporters can improve the formulation design and clinical application of cationic drugs.

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  • In this study, the effects of Tween 40 and ethanol supplementation on the secretion, structure and antioxidant activities of exopolysaccharide (EPS) from Inonotus rickii were investigated. It was observed that Tween 40 and ethanol displayed a stimulatory effect on EPS secretion. The EPSs obtained by the addition of Tween 40 (EPS-T), ethanol (EPS-E) and control (EPS-C) were purified by Sepharose CL-6B gel chromatography and molecular weights of EPS-T, EPS-E and EPS-C were estimated to be 22.1, 30.0, and 40.5 kDa, respectively. Monosaccharide composition analysis indicated that EPS-T, EPS-E and EPS-C were mainly composed of mannose and glucose. Furthermore, EPS-E exhibited better OH• and DPPH scavenging activities than those of EPS-C and EPS-T, which might be associated with its molecular characterization.

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  • L-ornithine is a valuable amino acid with a wide range of applications in the pharmaceutical and food industries. However, the production of L-ornithine by fermentation cannot compete with other methods, because of the low titers produced with this technique. Development of fermentation techniques that result in a high yield of L-ornithine and efficient strategies for improving L-ornithine production are essential.

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  • Dispersants including Tween 20, Tween 40, Tween 60, and polyacrylic acid (PAA) were used to modify nanoscale zero-valent iron (nZVI). All dispersants dispersed nZVI effectively. PAA-modified nZVI was more stable than nZVI that was modified with Tween surfactant. Iron nanoparticles that were prepared using 0.5-5.0% (vol%) of PAA remained in suspension for more than 2 h. nZVI that was modified using Tween surfactant remained in suspension for 30-60 min, and there was complete sedimentation of bare iron in 10 min. When 2.0-5.0% (vol%) of Tween surfactant was used, the stability of the nZVI that was modified using Tween 20 was much better than that for nZVI that was modified using Tween 40 or Tween 60. The results for the transportation test show that nZVI that was prepared using 2% (vol%) of Tween 20 exhibited the best mobility in porous media. Approximately 83-90% of TCE was degraded by bare, PAA-modified, and Tween 20-modified nZVI, and about 63-67% of TCE was removed by nZVI that was modified using Tween 40 and Tween 60 during 20 days of reaction. The production of cis-dichloroethene (DCE) and 1,1-DCE demonstrates that TCE is removed via reductive dechlorination. The results of this study show that PAA- and Tween 20-modified nZVI are more practical for in situ remediation because they exhibit good mobility and degrade TCE effectively.

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  • Understanding the bioactive partitioning between the phases of an emulsion system underpins strategies for improving the efficiency of bioactive protection against degradation. We analysed partitioning of β-carotene in emulsions with various formulations in-situ using confocal Raman microscopy (CRM). The partitioning of β-carotene into the aqueous phase of emulsions increased when whey protein isolate (WPI) was heat or high pressure-treated prior to emulsion formation. However, increasing the concentration of high pressure-treated WPI reduced the β-carotene partitioning into the aqueous phase. Increasing the solid fat content in the carrier oil favoured the migration of β-carotene into the aqueous phase. The use of WPI as the emulsifier resulted in a greater partitioning of β-carotene into the aqueous phase compared to when Tween 40 was the emulsifier. This study demonstrates that partitioning of β-carotene between the aqueous and oil phase is dependent on the characteristics of the oil phase, emulsifier type and processing.

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  • Two O/W forskolin-loaded nano-emulsions (0.075% wt.) based on medium chain triglycerides (MCT) and stabilized by a nonionic surfactant (Polysorbate 80 or Polysorbate 40) were studied as forskolin delivery systems. The nano-emulsions were prepared by the PIC method. The mean droplet size of the nano-emulsions with Polysorbate 80 and Polysorbate 40 with oil/surfactant (O/S) ratios of 20/80 and 80% water concentration, measured by Dynamic Light Scattering (DLS), was of 118 nm and 111 nm, respectively. Stability of the formulations, as assessed by light backscattering for 24 h, showed that both nano-emulsions were stable at 25°C. Studies of forskolin in vitro skin permeation from the nano-emulsions and from a triglyceride solution were carried out at 32°C, using Franz-type diffusion cells. A mixture of PBS/ethanol (60/40 v/v) was used as a receptor solution. The highest flux and permeability coefficient was obtained for the system stabilized with Polysorbate 80 (6.91±0.75 µg · cm·h and 9.21 · 10±1.00 · 10 cm · h, respectively) but no significant differences were observed with the flux and permeability coefficient value of forskolin dissolved in oil. The obtained results showed that the nano-emulsions developed in this study could be used as effective carriers for topical administration of forskolin.

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  • A highly sensitive and selective ratiometric sensor for the quantification of cyanide (CN) in aqueous samples has been developed using spherical gold nanoparticles (AuNPs) stabilized by polysorbate 40 (PS-40). Three different AuNP sizes (14, 40 and 80nm mean diameters) were used to evaluate the response of the sensor using both colorimetric and Resonance Rayleigh Scattering (RRS) detection schemes. The best results were obtained for the sensor using 40nm AuNPs, for which the limits of detection (LODs) were found to be 100nmolL in a benchtop instrument and 500nmolL by the naked eye, values well below the maximum acceptable level for drinking water (1.9µmolL) set by the World Health Organization (WHO). The practical use of the 40nm-AuNPs RRS sensor was demonstrated with the determination of CN in drinking and fresh waters. Finally, the sensor was successfully implemented in a compact portable device consisting of two light-emitting diodes (LEDs) and a miniature spectrometer, turning this sensor into a very potent tool for its application as a quick routine field-deployable analytical method.

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  • Due to a relatively small size of bile acid salts, their mixed micelles with nonionic surfactants are analysed. Of the special interests are real binary mixed micelles that are thermodynamically more stable than ideal mixed micelles. Thermodynamic stability is expressed with an excess Gibbs energy (G) or over an interaction parameter (β). In this paper sodium salts of cholic (C) and hyodeoxycholic acid (HD) in their mixed micelles with Tween 40 (T40) are analysed by potentiometric titration and their pKa values are determined. Examined bile acids in mixed micelles with T40 have higher pKa values than free bile acids. The increase of ΔpKa acid constant of micellary bound C and HD is in a correlation with absolute values of an interaction parameter. According to an interaction parameter and an excess Gibbs energy, mixed micelle HD-T40 are thermodynamically more stable than mixed micelles C-T40. ΔpKa values are higher for mixed micelles with Tween 40 whose second building unit is HD, related to the building unit C. In both micellar systems, ΔpKa increases with the rise of a molar fraction of Tween 40 in binary mixtures of surfactants with sodium salts of bile acids. This suggests that, ΔpKa can be a measure of a thermodynamic stabilization of analysed binary mixed micelles as well as an interaction parameter. ΔpKa values are confirmed by determination of a distribution coefficient of HD and C in systems: water phase with Tween 40 in a micellar concentration and 1-octanol, with a change of a pH value of a water phase. Conformational analyses suggests that synergistic interactions between building units of analysed binary micelles originates from formation of hydrogen bonds between steroid OH groups and polyoxyethylene groups of the T40. Relative similarity and spatial orientation of C and C OH group allows cooperative formation of hydrogen bonds between T40 and HD - excess entropy in formation of mixed micelle. If a water solution of analysed binary mixtures of surfactants contains urea in concentration of 4M significant decreases of an interaction parameter value happens which confirms the importance of hydrogen bonds in synergistic interactions (urea compete in hydrogen bonds).

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