SciCombinator

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Concept: Polysorbate

168

Tween 80 (polysorbate 80) has been used as a reducing agent and protecting agent to prepare stable water-soluble silver nanoparticles on a large scale through a one-pot process, which is simple and environmentally friendly. Silver ions can accelerate the oxidation of Tween 80 and then get reduced in the reaction process. The well-ordered arrays such as ribbon-like silver nanostructures could be obtained by adjusting the reaction conditions. High-resolution transmission electron microscopy confirms that ribbon-like silver nanostructures (approximately 50 nm in length and approximately 2 mum in width) are composed of a large number of silver nanocrystals with a size range of 2 to 3 nm. In addition, negative absorbance around 320 nm in the UV-visible spectra of silver nanoparticles has been observed, probably owing to the instability of nanosized silver colloids.

Concepts: Electron, Hydrogen, Redox, Oxidizing agent, Nanotechnology, Reducing agent, Polysorbate 80, Polysorbate

138

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 25ºC. Studies of forskolin in vitro skin permeation from the nano-emulsions and from a triglyceride solution were carried out at 32ºC, 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-2·h-1 and 9.21·10-3±1.00·10-3 cm·h-1, 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.

Concepts: Fatty acid, Surfactant, Colloidal chemistry, Light scattering, Dynamic light scattering, Polysorbate 80, Polysorbate, Polysorbate 20

29

Escherichia coli biotype O104:H4 recently caused the deadliest E. coli outbreak ever reported. Based on prior results, it was hypothesized that compounds inhibiting biofilm formation by O104:H4 would reduce its pathogenesis. The nonionic surfactants polysorbate 80 (PS80) and polysorbate 20 (PS20) were found to reduce biofilms by ≥ 90% at submicromolar concentrations and elicited nearly complete dispersal of preformed biofilms. PS80 did not significantly impact in vivo colonization in a mouse infection model; however, mice treated with PS80 exhibited almost no intestinal inflammation or tissue damage while untreated mice exhibited robust pathology. As PS20 and PS80 are classified as ‘Generally Recognized as Safe’ (GRAS) compounds by the Food and Drug Administration (FDA), these compounds have clinical potential to treat future O104:H4 outbreaks.

Concepts: Bacteria, Model organism, Escherichia coli, Enterobacteriaceae, Biofilm, Polysorbate 80, Polysorbate, Polysorbate 20

28

Nanostructured lipid carriers (NLC) composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. Before NLC can be used as drug carriers, the cytotoxicity of their components must be ascertained. The cytotoxicity of solid lipids (trilaurin, palmitin, docosanoid acid and hydrogenated palm oil [HPO]) and surfactants (Polysorbate 20, 80 and 85) were determined on BALB/c 32 3T3 cells. The HPO and Polysorbate 80 were least cytotoxic and used with olive oil in the formulation of NLC. The particle size, polydispersity index, zeta potential, specific surface area and crystallinity index of the NLC were 61.14 nm, 0.461, -25.4 mV and 49.07 m2 and 27.12% respectively, while the melting point was 4.3 °C lower than of 36 HPO. Unlike in serum-free, NLC incubated in fetal bovine serum-supplemented medium did not show particle growth, suggesting that serum proteins in medium 38 inhibit nanoparticles aggregation. The study also showed that NLC was less toxic to BALB/c 3T3 cells than Polysorbate 80. Thus, NLC with olive oil, HPO and 40 Polysorbate 80 as components are potentially good drug carriers with minimal cytotoxicity on normal cells.

Concepts: Protein, Colloid, Cytotoxicity, Liquid, Trans fat, Colloidal chemistry, Polysorbate 80, Polysorbate

28

A differential scanning fluorimetry (DSF) based high-throughput screening assay with the fluorescent molecular rotor CCVJ (9-(2-carboxy-2-cyanovinyl)julolidine) was developed. CCVJ is mainly sensitive to viscosity and less to polarity in comparison to polarity-sensitive dyes like SYPRO Orange, which was commonly used in DSF measurements. Therefore DSF with CCVJ is a suitable approach for high-throughput screening and stability testing of surfactant-containing protein formulations. Due to the different detection principles of CCVJ and SYPRO Orange, the midpoint of the fluorescence curve of CCVJ, defined as temperature of aggregation (Tagg), was obtained at a higher temperature than the midpoint of the SYPRO Orange fluorescence curve, defined as temperature of hydrophobic exposure (Th). Granulocyte colony stimulating factor (G-CSF) was used as model protein for all measurements. Commonly used surfactants in therapeutic protein formulations (polysorbate 20, polysorbate 80 and poloxamer 188) were investigated by DSF with CCVJ and SYPRO Orange. The fluorescence properties of CCVJ were minimally affected by investigated surfactants at concentrations typically used in pharmaceutical protein formulations. SYPRO Orange however, showed high background fluorescence as it also interacts with hydrophobic groups of surfactants. CCVJ was also capable of detecting thermally induced aggregation in the commercial polysorbate 80-containing product Neupogen®.

Concepts: Protein, Fluorescence, Oxygen, Molecular biology, Fluorescence spectroscopy, Polysorbate 80, Polysorbate, Polysorbate 20

27

The effects of selected nonionic emulsifiers on the physicochemical characteristics of astaxanthin nanodispersions produced by an emulsification/evaporation technique were studied. The emulsifiers used were polysorbates (Polysorbate 20, Polysorbate 40, Polysorbate 60 and Polysorbate 80) and sucrose esters of fatty acids (sucrose laurate, palmitate, stearate and oleate). The mean particle diameters of the nanodispersions ranged from 70 nm to 150 nm, depending on the emulsifier used. In the prepared nanodispersions, the astaxanthin particle diameter decreased with increasing emulsifier hydrophilicity and decreasing carbon number of the fatty acid in the emulsifier structure. Astaxanthin nanodispersions with the smallest particle diameters were produced with Polysorbate 20 and sucrose laurate among the polysorbates and the sucrose esters, respectively. We also found that the Polysorbate 80- and sucrose oleate-stabilized nanodispersions had the highest astaxanthin losses (i.e., the lowest astaxanthin contents in the final products) among the nanodispersions. This work demonstrated the importance of emulsifier type in determining the physicochemical characteristics of astaxanthin nano-dispersions.

Concepts: Fatty acid, Fat, Ester, Hydrolysis, Polysorbate 80, Polysorbate, Polysorbate 20, Non-ionic surfactants

24

An ionic liquid (IL)-modified micellar electrokinetic chromatography (MEKC) method was proposed for the separation and determination of eight phenolic acids. In order to increase separation efficiency and selectivity, the micelle system consisting of aqueous mixtures of ILs, Tween 20 and borate was optimized using a D-optimal design. A 16-run experimental plan was carried out. The results indicated that the addition of ILs in background electrolyte could significantly alter the electrophoretic behavior and improve the resolution of target analytes. By evaluating the electropherograms obtained, a satisfactory separation condition for all analytes was achieved in 10min with optimized buffer composed of 0.70% (w/w) 1-butyl-3-methylimidazolium tetrafluoroborate, 8.1% (w/w) polyoxyethylene sorbitan monolaurate (Tween 20) and 10mM sodium borate at pH 9.2. Under these conditions, all calibration curves showed good linearity (r(2)>0.9969), and accuracy (recoveries ranging from 94.71 to 106.85%). Finally, the proposed method was successfully applied to determine the phenolic acids in a Chinese medicine compound, compound danshen dripping pills.

Concepts: Chromatography, Analytical chemistry, PH, Capillary electrophoresis, Micellar electrokinetic chromatography, Borax, Buffer solution, Polysorbate

0

The aim of the present work was to investigate the ability of nonionic surfactants to increase the oral absorption of the P-glycoprotein substrate etoposide in vitro and in vivo. Intestinal absorption was investigated by studying bidirectional permeability of etoposide across filter-grown Caco-2 and MDCKII MDR1 cell monolayers. The oral absorption of etoposide was investigated in wild type (WT) and mdr1a deficient (KO) Sprague-Dawley rats. In cell cultures, polysorbate 20 (PS20) decreased P-glycoprotein mediated efflux of etoposide. When PS20 and etoposide were co-administered to WT rats, the oral absorption of etoposide increased significantly in the presence of 5 and 25% (v/v) PS20. However, in KO rats, the exposure of etoposide after oral co-administration with 5% PS20 was similar to control. Unexpectedly, co-administration of etoposide with 25% PS20 significantly reduced the absorption fraction of etoposide in mdr1a KO rats. In vitro dialysis studies performed on PS20-containing etoposide solutions suggested that the reduced bioavailability may be due to etoposide retention in PS20 micelles and/or through increased viscosity. In conclusion, PS20 increases oral bioavailability of etoposide through inhibition of P-glycoprotein. However, the use of the excipient may be challenged by etoposide retention at higher concentrations.

Concepts: Cell, Enzyme, In vivo, In vitro, Surfactant, Pharmacokinetics, Polysorbate, P-glycoprotein

0

Polyoxyethylene (20) sorbitan monooleate (Tween 80) can be incorporated into the gel-like phase formed by L-α-phosphatidylcholine (PC) and dioctyl sulfosuccinate sodium salt (DOSS) for potential application as a gel-like dispersant for oil spill treatment. Such gel-like dispersants offer advantages over existing liquid dispersants for mitigating oil spill impacts.

Concepts: Water, Sodium chloride, Sodium, Salt, Exxon Valdez oil spill, Polysorbate, Detergent, Dispersant

0

Deformability is not just a fundamentally interesting vesicle characteristic; it is also the key determinant of vesicle ability to cross the skin barrier; i.e. skin penetrability. Development of bilayer vesicles for drug and vaccine delivery across the skin should hence involve optimization of this property, which is controllable by the concentration of bilayer softeners in or near the vesicle bilayers. To this end, we propose a simple method for quantifying the effect of bilayer softeners on deformability of bilayer vesicles. The method derives the bending rigidity of vesicle bilayers from vesicle size dependence on softener concentration. To exemplify the method, we studied mixtures of soybean phosphatidylcholine with anionic sodium deoxycholate, non-ionic polyoxyethylene (20) sorbitan oleyl ester (polysorbate 80), or non-ionic polyoxyethylene (20) oleyl ether (C18:1EO20, Brij(®) 98). The bending rigidity of resulting mixed-amphipat vesicle bilayers decreased quasi-exponentially as the concentration of the bilayer softener increased, as one would expect on theoretical ground. The bilayer bending rigidity reached low value, near the thermal stability limit, i.e. kBT, before vesicle transformation into non-vesicular aggregates begins. For a soybean phosphatidylcholine concentration of 5.0mmolkg(-1), the bilayer bending rigidity reached 1.5 kBT at a total deoxycholate concentration of 4.1mmolkg(-1) and 3.4 kBT at a total polysorbate 80 concentration of 2.0mmolkg(-1). In the case of C18:1EO20, the bilayer bending rigidity reached 1.5 kBT at bilayer surface occupancy α=0.1. The dependence of vesicle size on the bilayer softener concentration thus reveals vesicle transformation into different aggregate structures (such as mixed micelles with poor skin penetrability) and practically valuable information on vesicle deformability. Our results compare favorably with results of literature measurements. We provide practical guidance to using the new analytical method to optimize deformable vesicle formulations.

Concepts: Archaea, Aggregate, Micelle, Vesicle, Deoxycholic acid, Polysorbate, Derivation