Novel magnetic iron oxide nanoparticles coated with poly(ethylene imine)-g-poly(ethylene glycol) for potential biomedical application: synthesis, stability, cytotoxicity and MR imaging

Magnetic iron oxide nanoparticles have found application as contrast agents for magnetic resonance imaging (MRI) and as switchable drug delivery vehicles. Their stabilization as colloidal carriers remains a challenge. The potential of poly(ethylene imine)-g-poly(ethylene glycol) (PEGPEI) as stabilizer for iron oxide (γ-Fe₂O₃) nanoparticles was studied in comparison to branched poly(ethylene imine) (PEI). Carrier systems consisting of γ-Fe₂O₃-PEI and γ-Fe₂O₃-PEGPEI were prepared and characterized regarding their physicochemical properties including magnetic resonance relaxometry. Colloidal stability of the formulations was tested in several media and cytotoxic effects in adenocarcinomic epithelial cells were investigated. Synthesized γ-Fe₂O₃ cores showed superparamagnetism and high degree of crystallinity. Diameters of polymer-coated nanoparticles γ-Fe₂O₃-PEI and γ-Fe₂O₃-PEGPEI were found to be 38.7 ± 1.0 nm and 40.4 ± 1.6 nm, respectively. No aggregation tendency was observable for γ-Fe₂O₃-PEGPEI over 12 h even in high ionic strength media. Furthermore, IC₅₀ values were significantly increased by more than 10-fold when compared to γ-Fe₂O₃-PEI. Formulations exhibited r₂ relaxivities of high numerical value, namely around 160 mM⁻¹ s⁻¹. In summary, novel carrier systems composed of γ-Fe₂O₃-PEGPEI meet key quality requirements rendering them promising for biomedical applications, e.g. as MRI contrast agents.

Comparative stability studies of poly(2-methyl-2-oxazoline) and poly(ethylene glycol) brush coatings

Non-fouling surfaces that resist non-specific adsorption of proteins, bacteria, and higher organisms are of particular interest in diverse applications ranging from marine coatings to diagnostic devices and biomedical implants. Poly(ethylene glycol) (PEG) is the most frequently used polymer to impart surfaces with such non-fouling properties. Nevertheless, limitations in PEG stability have stimulated research on alternative polymers that are potentially more stable than PEG. Among them, we previously investigated poly(2-methyl-2-oxazoline) (PMOXA), a peptidomimetic polymer, and found that PMOXA shows excellent anti-fouling properties. Here, we compare the stability of films self-assembled from graft copolymers exposing a dense brush layer of PEG and PMOXA side chains, respectively, in physiological and oxidative media. Before media exposure both film types prevented the adsorption of full serum proteins to below the detection limit of optical waveguide in situ measurements. Before and after media exposure for up to 2 weeks, the total film thickness, chemical composition, and total adsorbed mass of the films were quantified using variable angle spectroscopic ellipsometry (VASE), X-ray photoelectron spectroscopy (XPS), and optical waveguide lightmode spectroscopy (OWLS), respectively. We found (i) that PMOXA graft copolymer films were significantly more stable than PEG graft copolymer films and kept their protein-repellent properties under all investigated conditions and (ii) that film degradation was due to side chain degradation rather than due to copolymer desorption.

THERMORESPONSIVE PROPERTIES OF GOLD HYBRID NANOPARTICLES OF POLY(DI(ETHYLENE GLYCOL) METHYL ETHER METHACRYLATE) (PDEGMA) AND ITS BLOCK COPOLYMERS WITH DIFFERENT ANCHORING REGIMES

Thermo-responsive materials have been of interest for many years, and have been studied mostly as thermally stimulated drug delivery vehicles. Recently acrylate and methacrylates with pendant ethylene glycol methyl ethers been studied as thermo responsive materials. This work explores thermo response properties of hybrid nanoparticles of one of these methacrylates (DEGMA) and a block copolymer with one of the acrylates (OEGA), with gold nanoparticle cores of different sizes. We were interested in the effects of gold core size, number and type of end groups that anchored the chains to the gold cores, and location of bonding sites on the thermo-response of the polymer. To control the number and location of anchoring groups we using a type of controlled radical polymerization called Reversible Addition Fragmentation Transfer (RAFT) Polymerization. Smaller gold cores did not show the thermo responsive behavior of the polymer but the gold cores did seem to self-assemble. Polymer anchored to larger gold cores did show thermo responsivity. The anchoring end group did not alter the thermoresponsivity but thiol-modified polymers stabilized gold cores less well than chains anchored by dithioester groups, allowing gold cores to grow larger. Use of multiple bonding groups stabilized the gold core. Using block copolymers we tested the effects of number of thiol groups and the distance between them. We observed that the use of multiple anchoring groups on the block copolymer with a sufficiently large gold core did not prevent thermo responsive behavior of the polymer to be detected which allows a new type of thermo-responsive hybrid nanoparticle to be used and studied for new applications.

Whole body postmortem angiography with a high viscosity contrast agent solution using poly ethylene glycol as contrast agent dissolver

Postmortem minimal invasive angiography has already been implemented to support virtual autopsy examinations. An experimental approach in a porcine model to overcome an initially described artificial tissue edema artifact by using a poly ethylene glycol (PEG) containing contrast agent solution showed promising results. The present publication describes the first application of PEG in a whole corpse angiographic CT examination. A minimal invasive postmortem CT angiography was performed in a human corpse utilizing the high viscosity contrast agent solution containing 65% of PEG. Injection was carried out via the femoral artery into the aortic root in simulated cardiac output conditions. Subsequent CT scanning delivered the 3D volume data of the whole corpse. Visualization of the human arterial anatomy was excellent and the contrast agent distribution was generally limited to the arterial system as intended. As exceptions an enhancement of the brain, the left ventricular myocardium and the renal cortex became obvious. This most likely represented the stage of centralization of the blood circulation at the time of death with dilatation of the precapillary arterioles within these tissues. Especially for the brain this resulted in a distinctively improved visualization of the intracerebral structures by CT. However, the general tissue edema artifact of postmortem minimal invasive angiography examinations could be distinctively reduced.

Bovine primary chondrocyte culture in synthetic matrix metalloproteinase-sensitive poly(ethylene glycol)-based hydrogels as a scaffold for cartilage repair

A poly(ethylene glycol) (PEG)-based hydrogel was used as a scaffold for chondrocyte culture. Branched PEG-vinylsulfone macromers were end-linked with thiol-bearing matrix metalloproteinase (MMP)-sensitive peptides (GCRDGPQGIWGQDRCG) to form a three-dimensional network in situ under physiologic conditions. Both four- and eight-armed PEG macromer building blocks were examined. Increasing the number of PEG arms increased the elastic modulus of the hydrogels from 4.5 to 13.5 kPa. PEG-dithiol was used to prepare hydrogels that were not sensitive to degradation by cell-derived MMPs. Primary bovine calf chondrocytes were cultured in both MMP-sensitive and MMP-insensitive hydrogels, formed from either four- or eight-armed PEG. Most (>90%) of the cells inside the gels were viable after 1 month of culture and formed cell clusters. Gel matrices with lower elastic modulus and sensitivity to MMP-based matrix remodeling demonstrated larger clusters and more diffuse, less cell surface-constrained cell-derived matrix in the chondron, as determined by light and electron microscopy. Gene expression experiments by real-time RT-PCR showed that the expression of type II collagen and aggrecan was increased in the MMP-sensitive hydrogels, whereas the expression level of MMP-13 was increased in the MMP-insensitive hydrogels. These results indicate that cellular activity can be modulated by the composition of the hydrogel. This study represents one of the first examples of chondrocyte culture in a bioactive synthetic material that can be remodeled by cellular protease activity.

Measurements of attractive forces between proteins and end-grafted poly(ethylene glycol) chains

The surface force apparatus was used to measure directly the molecular forces between streptavidin and lipid bilayers displaying grafted Mr 2,000 poly(ethylene glycol) (PEG). These measurements provide direct evidence for the formation of relatively strong attractive forces between PEG and protein. At low compressive loads, the forces were repulsive, but they became attractive when the proteins were pressed into the polymer layer at higher loads. The adhesion was sufficiently robust that separation of the streptavidin and PEG uprooted anchored polymer from the supporting membrane. These interactions altered the properties of the grafted chains. After the onset of the attraction, the polymer continued to bind protein for several hours. The changes were not due to protein denaturation. These data demonstrate directly that the biological activity of PEG is not due solely to properties of simple polymers such as the excluded volume. It is also coupled to the competitive interactions between solvent and other materials such as proteins for the chain segments and to the ability of this material to adopt higher order intrachain structures.

Synthesis of palladium nanoparticles over graphite oxide and carbon nanotubes by reduction in ethylene glycol and their catalytic performance on the chemoselective hydrogenation of para-chloronitrobenzene

Pd nanoparticles have been synthesized over carbon nanotubes (CNT) and graphite oxide (GO) by reduction with ethylene glycol and by conventional impregnation method. The catalysts were tested on the chemoselective hydrogenation of p-chloronitrobenzene and the effect of the synthesis method and surface chemistry on their catalytic performance was evaluated. The catalysts were characterized by N2 adsorption/desorption isotherms at 77 K, TEM, powder X-ray diffraction, thermogravimetry, infrared and X-ray photoelectron spectroscopy and ICP-OES. It was observed that the synthesis of Pd nanoparticles employing ethylene glycol resulted in metallic palladium particles of smaller size compared to those prepared by the impregnation method and similar for both supports. The presence of oxygen groups on the support surface favored the activity and diminished the selectivity. It seems that ethylene glycol reacted with the surface groups of GO, this favoring the selectivity. The activity was higher over the CNT-based catalysts and both catalysts prepared by reduction in ethylene glycol were quite stable upon recycling.

Analysis of the phase behavior of the aqueous poly(ethylene glycol)-Ficoll system

The PEG-Ficoll polymer phase system is one that has been overlooked in the past for biotechnology applications because of the stability of its emulsions. However, new applications, such as emulsion coating of cells, are appearing that rely on this very property. Ficoll is highly polydisperse and multimodal with three distinct Ficoll peaks in gel permeation chromatography. As a result, the transition between one-phase and two-phase systems is blurred and the binodials obtained through turbidometric titration and tie-line analysis differ significantly. Moreover, since the three Ficoll peaks partition differently, tie-line analysis cannot be described by a simple model of the aqueous two-phase system. A simple modification to the model allowed for excellent fit, and this modification may prove well-suited for the many practical cases where aqueous two-phase systems fail to display parallel tie-lines as implicitly assumed in the simpler model.

Corrosion behaviour of magnesium in ethylene glycol

Corrosion of magnesium engine components by coolant is an important issue in the automotive industry where magnesium alloys may be used. It is of significance to understand the corrosion behaviour of pure magnesium in ethylene glycol solutions, as this can provide a basis for developing new coolants for magnesium alloy engine blocks. In this paper, through corrosion and electrochemical tests, it was found that the corrosion rate of magnesium decreased with increasing concentration of ethylene glycol. Individual contaminants, such as NaCl, NaHCO3, Na2SO4 and NaCl can make aqueous ethylene glycol solution more corrosive to magnesium. However, in NaCl contaminated ethylene glycol, NaHCO3 and Na2SO4 showed some inhibition effect. The solution resistivity played an important role in the corrosion of magnesium in ethylene glycol solutions, and the competitive adsorption of ethylene glycol and the contaminants on the magnesium surface was also responsible for the observed corrosion behaviours. The corrosion of magnesium in ethylene glycol can be effectively inhibited by addition of fluorides that react with magnesium and form a protective film on the surface. (C) 2003 Elsevier Ltd. All rights reserved.

Phase behavior, crystallization, and morphology in thermosetting blends of a biodegradable poly(ethylene glycol)-type epoxy resin and poly(ε-caprolactone)

Thermosetting blends of a biodegradable poly(ethylene glycol)-type epoxy resin (PEG-ER) and poly(epsilon-caprolactone) (PCL) were prepared via an in situ curing reaction of poly(ethylene glycol) diglycidyl ether (PEGDGE) and maleic anhydride (MAH) in the presence of PCL. The miscibility, phase behavior, crystallization, and morphology of these blends were investigated. The uncured PCL/PEGDGE blends were miscible, mainly because of the entropic contribution, as the molecular weight of PEGDGE was very low. The crystallization and melting behavior of both PCL and the poly(ethylene glycol) (PEG) segment of PEGDGE were less affected in the uncured PCL/PEGDGE blends because of the very close glass-transition temperatures of PCL and PEGDGE. However, the cured PCL/PEG-ER blends were immiscible and exhibited two separate glass transitions, as revealed by differential scanning calorimetry and dynamic mechanical analysis. There existed two phases in the cured PCL/PEG-ER blends, that is, a PCL-rich phase and a PEG-ER crosslinked phase composed of an MAH-cured PEGDGE network. The crystallization of PCL was slightly enhanced in the cured blends because of the phase-separated nature; meanwhile, the PEG segment was highly restricted in the crosslinked network and was noncrystallizable in the cured blends. The phase structure and morphology of the cured PCL/PEG-ER blends were examined with scanning electron microscopy; a variety of phase morphologies were observed that depended on the blend composition. (C) 2004 Wiley Periodicals, Inc.

Gold nanoparticles decorated with oligo(ethylene glycol) thiols:enhanced Hofmeister effects in colloid−protein mixtures

Oligo(ethylene glycol) (OEG) thiol self-assembled monolayer (SAM) decorated gold nanoparticles (AuNPs) have potential applications in bionanotechnology due to their unique property of preventing the nonspecific absorption of protein on the colloidal surface. For colloid-protein mixtures, a previous study (Zhang et al. J. Phys. Chem. A 2007, 111, 12229) has shown that the OEG SAM-coated AuNPs become unstable upon addition of proteins (BSA) above a critical concentration, c*. This has been explained as a depletion effect in the two-component system. Adding salt (NaCl) can reduce the value of c*; that is, reduce the stability of the mixture. In the present work, we study the influence of the nature of the added salt on the stability of this two-component colloid-protein system. It is shown that the addition of various salts does not change the stability of either protein or colloid in solution in the experimental conditions of this work, except that sodium sulfate can destabilize the colloidal solutions. In the binary mixtures, however, the stability of colloid-protein mixtures shows significant dependence on the nature of the salt: chaotropic salts (NaSCN, NaClO4, NaNO3, MgCl2) stabilize the system with increasing salt concentration, while kosmotropic salts (NaCl, Na2SO4, NH4Cl) lead to the aggregation of colloids with increasing salt concentration. These observations indicate that the Hofmeister effect can be enhanced in two-component systems; that is, the modification of the colloidal interface by ions changes significantly the effective depletive interaction via proteins. Real time SAXS measurements confirm in all cases that the aggregates are in an amorphous state.

Degradable poly(ethylene glycol)-based hydrogels:synthesis, physico-chemical properties and in vitro characterization

Designing degradable hydrogels is complicated by the structural and temporal complexities of the gel and evolving tissue. A major challenge is to create scaffolds with sufficient mechanical properties to restore initial function while simultaneously controlling temporal changes in the gel structure to facilitate tissue formation. Poly(ethylene glycol) was used in this work, to form biodegradable poly(ethylene glycol)-based hydrogels with hydrolyzable poly-l-lactide segments in the backbone. Non-degradable poly(ethylene glycol) was also introduced in the formulation to obtain control of the degradation profile that encompasses cell growth and new tissue formation. The dependence on polymer composition was observed by higher degradation profiles and decreased mechanical properties as the content of degradable segments was increased in the formulation. Based on in vitro tests, no toxicity of extracts or biomaterial in direct contact with human adipose tissue stem cells was observed, and the ultraviolet light treatment did not affect the proliferation capacity of the cells.