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A stabilized high drug load intravenous formulation could allow compounds with less optimal pharmacokinetic profiles to be developed. Polyethylene glycol (PEG)-ylation is a frequently used strategy for particle delivery systems to avoid the liver, thereby extending blood circulation time. The present work reports the mouse in vivo distribution after i.v. administration of a series of nanocrystals prepared with the bead milling technique and PEG-ylated with DSPE-PEG2000 and Pluronic F127, with and without polyvinylpyrrolidone K30 (PVP)/Aerosol OT (AOT) as primary stabilizers. While all formulations were cleared significantly faster than expected from nanocrystal dissolution alone, purely DSPE-PEG2000 PEG-ylated particles displayed prolonged circulation time (particles elimination half-life of 9min) compared to DSPE-PEG2000/PVP/AOT formulation (half-life of 3min). The two Pluronic F127 stabilized formulations displayed similar half-lives (9min with and without PVP/AOT, respectively). Whole tissue kinetics shows that clearance of particles could be attributed to accumulation in the liver. A separate in vivo study addressed the liver cell distribution after administration. Dissolved compound accumulated in hepatocytes only, while particles were distributed between liver sinusoidal endothelial cells and Kupffer cells. More DSPE-PEG2000/PVP/AOT stabilized particles accumulated in the liver, preferably in Kupffer cells, compared to Pluronic F127/PVP/AOT stabilized particles. The present study extends the understanding of PEG-ylation and "stealth" behaviour to also include nanocrystals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This article describes the preparation and characterization of composites containing poly(ethylene- co-butyl acrylate) (EBA-13 and EBA-28 with 13 and 28 wt % butyl acrylate, respectively) and 2-12 wt % (0.5-3 vol %) of aluminum oxide nanoparticles (two types differing in specific surface area and hydroxyl-group concentration; uncoated and coated with, respectively, octyltriethoxysilane and aminopropyltriethoxysilane). A greater surface coverage was obtained with aminopropyltriethoxysilane than with octyltriethoxysilane. An overall good dispersion was obtained in the EBA-13 composites prepared by extrusion compounding. Composites with octyltriethoxysilane-coated nanoparticles showed the best dispersion. The addition of the nanoparticles to EBA-28 resulted in poor dispersion, probably due to insufficiently high shear forces acting during extrusion mixing which were unable to break down nanoparticle agglomerates. The nanoparticles had no effect on the crystallization kinetics in the EBA-13 composites, but in the EBA-28 composites the presence of the nanoparticles led to an increase in the crystallization peak temperature, suggesting that the nanoparticles had a nucleating effect in this particular polymer. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012 [ABSTRACT FROM AUTHOR]

Abstract: The antioxidant activity of Irganox 1010 (0.2wt%) in aluminium oxide (2–12wt%) – poly(ethylene-co-butyl acrylate) nanocomposites was studied. The aluminium oxide nanoparticles were in three different forms: uncoated and coated with either octyltriethoxysilane or aminopropyltriethoxysilane. The activity of the stabilizer in the nanocomposites was assessed by determining the oxidation induction time (OIT) using DSC. Composites with untreated aluminium oxide nanoparticles showed a much shorter OIT than the pristine polymer with the same overall antioxidant concentration indicating adsorption of the antioxidant onto the nanoparticle surfaces. The adsorption of antioxidant onto both uncoated and coated nanoparticles was confirmed by X-ray photoelectron spectroscopy. Composites containing coated nanoparticle fillers showed a significantly smaller depression of the OIT, indicating that the replacement of hydroxyl groups with organic silane tails decreased the concentration of available adsorption sites on the particle surfaces. Composites with a filler coated with a silane having terminal aliphatic amine groups showed an increased OIT with respect to that of the pristine polymer suggesting a synergistic on the stability effect between the antioxidant and the amine groups. The long-term activity of the stabilizer was assessed by measuring the OIT on samples after ageing in air at 90°C for 720h. The decrease in OIT with increasing ageing time of the nanocomposites was slower than for the unfilled polymer. A possible interpretation of these data is that the antioxidant was slowly released from the adsorption sites on extended ageing. [Copyright &y& Elsevier]

The influence of moisture on the dielectric properties of different types of poly (ethyleneco- butyl acrylate) filled with alumina nanoparticles was systematically investigated by varying the type of aluminum oxide, particle surface treatment and filler content (2, 6 and 12 wt%). The nanoparticles were either unmodified or surface-treated with either aminopropyl triethoxysilane or octyltriethoxy silane. The complex permittivity was measured with an IDA200 dielectric spectroscopy analyzer at applied voltage of 200 Vpeak with frequencies varying between 1 mHz and 1 kHz. The measurements were performed at 25°C and relative air humidities of 24, 54 and 86 %. In order to expand the frequency range the HP 4284A precision LCR meter was used for measuring sample impedance at the frequency range of 100 Hz to 1 MHz. From the frequency dependence of dielectric losses it can be seen that absorbed water plays a significant role in determining the dielectric properties of the nanocomposites. The magnitude of tan ? seems to be determined primarily by the particle size and filler content, while the peak frequency is mostly influenced by the amount of absorbed water and the type of particle coating. [ABSTRACT FROM AUTHOR]

The dielectric properties of poly (ethylene-co-butyl acrylate) with 13 wt% of butyl acrylate (EBA) filled with alumina nanoparticles were studied as a function of particle size, particle coating, filler content (2, 6 or 12wt%) and temperature. The particles were either unmodified or surface-treated with either aminopropyltriethoxy silane or octyltriethoxy silane. The complex permittivity was measured with frequencies varying between 1 mHz and up to 1 kHz at different temperatures (25, 45 and 65°C). Measurements were performed in dry conditions. From the dielectric spectroscopy measurements it can be seen that the tan ∂ for the dry samples is almost independent of the type of the particle coating used. It does, however, depend on the particle size, filler content and temperature. [ABSTRACT FROM AUTHOR]