Specific features of nonstoichiometric interpolymer complexes of poly(acrylic acid) and poly(ethylene glycol) as protectors of copper nanoparticles in aqueous sols

Advantages of interpolymer complexes for use as amphiphilic protectors of nanoparticles during the formation and stabilization of sols are considered. The effects of the ratio of poly(acrylic acid) and poly(ethylene glycol) and the molecular mass of poly(ethylene glycol) on the mean size and size distribution of copper nanoparticles in sols formed via the reduction of divalent copper ions in mixed aqueous solutions of these polymers are investigated. It is shown that sols of metal nanoparticles with small sizes and narrow size distributions are formed even when poly(ethylene glycols) with chain lengths below the “critical” chain length and a small PEG-to-PAA base-molar ratio are used. This is evidence for efficient protection of the formed copper nanoparticles by the interpolymer complex PEG-PAA under conditions of its instability and for self-organization of oligomeric PEG chains in complex macromolecular shields of nanoparticles.     

Meticulous Doxorubicin Release from pH-Responsive Nanoparticles Entrapped within an Injectable Thermoresponsive Depot

The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin-loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) in dimethyl sulfoxide solution into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.     

Binding enhancement of antigen-functionalized PEGylated gold nanoparticles onto antibody-immobilized surface by increasing the functionalized antigen using alpha-sulfanyl-omega-amino-PEG

We established a technique for constructing PEGylated gold nanoparticles (GNP) that have small compounds with almost complete functionalities on their surfaces using a newly synthesized hetero-telechelic poly(ethylene glycol) (PEG), and their association/dissociation behavior on an antibody-immobilized surface was evaluated using a surface plasmon resonance (SPR) sensor.     

Amphiphilic polymers as pseudotemplates in the synthesis of metal sols

The effects of poly(ethylene glycol) and its amphiphilic polymers on the products of copper ion reduction in aqueous solutions are studied. Whereas coarse metal dispersions are formed in poly(ethylene glycol) solutions, stable sols of metal nanoparticles with diameters of 2 nm and above are produced in the presence of poly(ethylene glycol monolaurate) and poly(ethylene glycol monostearate). A poly(ethylene glycol)-poly(propylene glycol) block copolymer (Pluronic) also stabilizes copper nanoparticles; however, the interaction product of this copolymer with nanoparticles forms a precipitate. According to the electron microscopy data, sol particles comprise polymer micelles containing included copper nanoparticles.     

Interactions of ADP-stimulated human platelets with PEGylated polystyrene substrates prepared by surface amidation

A study primarily focused on the interactions between ADP-stimulated human platelets and PEGylated polystyrene substrates is described in this paper. The platelet–surface interactions were investigated using colorimetric acid phosphatase assay. Two types of amine-containing polymeric hydrogel materials based on poly(ethylene glycol) (PEG), H₂N–PEG–OCH₃ and H₂N–PEG–NH₂, were used to PEGylate polystyrene surfaces derivatized with maleic anhydride by amidation at alkaline pH. In addition, comparative studies using surfaces non-covalently adsorbed by bovine serum albumin (BSA) or fibrinogen (Fg) were also conducted. The assay results showed that no significant platelet adhesion was observed when PEGylated surfaces or BSA-coated surfaces were exposed to unstimulated gel-filtered platelets (GFP). However, upon ADP-stimulation, platelet adhesion to the surfaces under investigation in this study all increased to varying degrees. Most importantly, the results showed that polystyrene surfaces PEGylated using H₂N–PEG–NH₂ were most effective in resisting platelet adhesion when assays were performed using ADP-stimulated GFP. By PEGylating the surfaces of polystyrene microtiter wells via the amidation reaction described in this paper, it is demonstrated that (i) higher degree of surface PEGylation is favored at more alkaline pH and (ii) polystyrene substrates capable of more effectively resisting the adhesion of ADP-stimulated GFP can be obtained by the PEGylation reaction carried out at pH 9.1 using H₂N–PEG–NH₂.     

Synthesis and characterization of lipid-polymer hybrid nanoparticles with pH-triggered poly(ethylene glycol) shedding

Novel lipid-polymer hybrid nanoparticles are designed with a poly(ethylene glycol) (PEG) coating that is shed in response to a low pH trigger. This allows the nanoparticles to be stable during systemic circulation and at neutral pH, but destabilize and fuse with lipid membranes in acidic environments. The hybrid nanoparticles consist of a poly(lactic-co-glycolic acid) core with a lipid and lipid-PEG monolayer shell. To make the hybrid nanoparticles pH sensitive, a lipid-(succinate)-mPEG conjugate is synthesized to provide a hydrolyzable PEG stealth layer that is shed off the particle surface at low pH. The pH-sensitivity of the nanoparticles is tunable using the molar concentration of the lipid-(succinate)-mPEG incorporated in the lipid shell of the particles. Possible uses of these pH-sensitive nanoparticles include aggregating in acidic tumor microenvironments, escaping acidified endosomes, or aggregating in deep lung tissue for improved inhalation administration.     

Interpolymer complexes of copolymers of vinyl ether of diethylene glycol with poly(acrylic acid)

 The complex formation reactions of poly(vinyl ether of diethylene glycol) as well as vinyl ether of diethylene glycol–vinyl butyl ether copolymers with poly(acrylic acid) have been studied in aqueous and alcohol solutions. The formation of interpolymer complexes which were stabilized by hydrogen bonds was shown. The effects of molecular weight of poly(acrylic acid) and the nature of the nonionic polymer on the composition and stability of interpolymer complexes were clarified. The critical pH values of complexation were determined for different systems with various molecular weights and hydrophobic–hydrophilic balances. The stability of the interpolymer complexes formed in aqueous and alcohol solutions with respect to dimethylformamide addition was evaluated. The role of hydrophobic interactions and the presence of active groups on stability of the interpolymer complexes is discussed. Received: 23 July 2001 Accepted: 27 September 2001     

Effect of copolymer composition on interpolymer complex formation of (co)poly(vinyl ether)s with poly(acrylic acid) in aqueous and organic solutions

The complex formation between vinyl ether of poly(ethylene glycol‐co‐vinyl butyl ether) with poly(acrylic acid) has been considered in aqueous and isopropanol solutions. The effect of copolymer composition on the complex formation process was clarified. It has been shown that the incorporation of hydrophobic fragments into macromolecules enhances the hydrophobic stabilization of polycomplexes in aqueous solutions. In organic media this effect disappears. The stability of polycomplexes formed both in aqueous and in organic solutions in respect to the addition of dimethylformamide has been studied.     

Electrokinetic characterization of poly(acrylic acid) and poly(ethylene oxide) brushes in aqueous electrolyte solutions

Surfaces carrying hydrophilic polymer brushes were prepared from poly(styrene)-poly(acrylic acid) and poly(styrene)-poly(ethylene oxide) diblock copolymers, respectively, using a Langmuir-Blodgett technique and employing poly(styrene)-coated planar glass as substrates. The electrical properties of these surfaces in aqueous electrolyte were analyzed as a function of pH and KCl concentration using streaming potential/streaming current measurements. From these data, both the zeta potential and the surface conductivity could be obtained. The poly(acrylic acid) brushes are charged due to the dissociation of carboxylic acid groups and give theoretical surface potentials of -160 mV at full dissociation in 10(-)(3) M solutions. The surface conductivity of these brushes is enormous under these conditions, accounting for more than 93% of the total measured surface conductivity. However, the mobility of the ions within the brush was estimated from the density of the carboxylic acid groups and the surface conductivity data to be only about 14% of that of free ions. The poly(ethylene oxide) (PEO) brushes effectively screen the charge of the underlying substrate, giving a very low zeta potential except when the ionic strength is very low. From the data, a hydrodynamic layer thickness of the PEO brushes could be estimated which is in good agreement with independent experiments (neutron reflectivity) and theoretical estimates. The surface conductivity in this system was slightly lower than that of the polystyren substrate. This also indicates that no significant amount of preferentially, i.e., nonelectrostatically attracted, ions taken up in the brush.     

Molecular structure and dynamics of poly(methacrylic acid) and poly(acrylic acid) complexes with dodecyl-substituted poly(ethylene glycol)

The molecular dynamics and the structure of molecular complexes formed by micelles of dodecyl-substituted poly(ethylene glycol) with poly(methacrylic acid) and poly(acrylic acid) in aqueous solutions were studied by viscosimetry, pH measurement, and electron spin resonance spin-probe techniques. At low surfactant concentrations, the conformation of the complex is a compact globule. The local mobility of surfactant molecules in such a complex is much slower than that in the free micelle. At high surfactant concentration, the nonionic micelles and polyacids form hydrophilic associates. The associates have the conformation of extended coils. In an associate, a major part of the micellar poly(ethylene glycol) groups is free. The local mobility of the micellar phase depends on the number of micelles involved in an associate. The mobility of surfactant molecules is slower in the complexes of poly(methacrylic acid) than in the complexes of poly(acrylic acid).     

Core-shell-corona au-micelle composites with a tunable smart hybrid shell

Micelles having a core of polystyrene and a mixed shell of poly(ethylene glycol) and poly(4-vinylpyridine) were formed through self-assembly of a triblock copolymer poly(ethylene glycol)- block-polystyrene- block-poly(4-vinylpyridine) in acidic water (pH 2). Reducing the HAuCl(4)-treated micelle solution leads to the formation of the Au-micelle composites with a core of polystyrene, a hybrid shell of poly(4-vinylpyridine)/Au/poly(ethylene glycol), and a corona of poly(ethylene glycol). The gold nanoparticles with controlled sizes were anchored to poly(4-vinylpyridine) to form the physically cross-linked hybrid shell. In aqueous solution, the hybrid shell is swollen and the swollen degree is sensitive to the pH condition. Under basic conditions, the channel in the hybrid shells of the composite is produced, which renders the composites a good catalytic activity. In addition, the composites also show good stability, unchanged hydrodynamic diameter, and surface plasmon absorption under different pH conditions.     

Protein PEGylation attenuates adsorption and aggregation on a negatively charged and moderately hydrophobic polymer surface

Covalent grafting of poly(ethylene glycol) chains to proteins ("PEGylation") is emerging as an effective technique to increase the in vivo circulation time and efficacy of protein drugs. PEGylated protein adsorption at a variety of solid/aqueous interfaces is a critical aspect of their manufacture, storage, and delivery. A special category of block copolymer, PEGylated proteins have one or more water-soluble linear polymer (PEG) blocks and a single globular protein block that each exert distinct intermolecular and surface interaction forces. We report the impact of PEGylation on protein adsorption at the interface between aqueous solutions and solid films of poly(lactide-co-glycolide) (PLG), a moderately hydrophobic and negatively charged polymer. Using the model protein lysozyme with controlled degrees of PEGylation, we employ total internal reflection fluorescence techniques to measure adsorption isotherms, adsorption reversibility, and the extent of surface-induced aggregation. Lysozyme PEGylation reduces the extent of protein adsorption and surface-induced aggregation and increases the reversibility of adsorption compared to the unconjugated protein. Results are interpreted in terms of steric forces among grafted PEG chains and their effects on protein-protein interactions and protein orientation on the surface.     

Rheological Properties of Hydrophobically Modified Poly(acrylic acid) in Mixed Solutions

Hydrophobically modified poly(acrylic acid) (HMPA) with single-tailed pendant side groups was prepared by precipitation polymerization. The effects of polymer concentration, surfactant and co-solvent on the solution properties of HMPA were investigated. HMPA solutions showed good viscosity enhancement and typical shear thinning behavior with increasing concentration. The surfactant TX-10 and co-solvent ethylene glycol gave rise to factors that changed the hydrophobic interactions and in turn the rheology behavior of the solutions. The transient associative network of HMPA in ethylene glycol + water mixed solutions was retained as the temperature was decreased to below 0 °C.     

PAA/PEO comb polymer effects on rheological properties and inter-particle forces in aqueous silica suspensions

The effects of a poly(acrylic acid) (PAA)-poly(ethylene) (PEO) comb polymer dispersant on the rheological properties and inter-particle forces in aqueous silica suspensions have been studied under varying pH conditions. The comb polymer was found to adsorb more strongly under acidic than basic conditions, indicating that the PAA backbone of the copolymer preferentially adsorbs onto silica surfaces with the PEO "teeth" extending out from the surface into the solution. In the presence of low concentrations of copolymer, the silica suspensions were stable due to electrostatic repulsions between the silica surfaces. At higher copolymer concentrations and under neutral and basic conditions, where the copolymer interacted only weakly with silica, the suspensions showed a transition from a dispersed to weakly flocculated state and attractive forces were measured between silica surfaces. Under acidic conditions, the silica dispersion also destabilized at intermediate copolymer adsorbed density and then was re-stabilized at higher adsorbed coverage. The silica suspensions were stable at high copolymer coverage due to steric repulsions between the particles. The destabilization at intermediate coverage is thought to be due to polymer bridging between particles or possibly depletion forces.     

Protein and Dye Adsorption on Poly(ethylene terephthalate) Nucleopore Membranes Modified with Polymers

Adsorption of basic, neutral, and acidic proteins on poly(ethylene terephthalate) nucleopore membranes was studied as a function of solution pH. Higher adsorption values were observed for basic and neutral proteins and lower, for acidic proteins. The value of pH corresponding to maximal adsorption was somewhat lower than the isoelectric points of proteins, thus suggesting that the adsorption was governed by a combination of ionic and hydrophobic interactions between proteins and the membrane surface. Proteins were adsorbed in an associated form. Membrane surface was modified with poly(ethylene imine) and poly(ethylene glycol). Combined modification of the membranes with these polymers was found to substantially decrease the adsorption of basic and neutral proteins, as well as basic dye and to slightly increase the adsorption of acidic proteins. The modifying coating had a high hydrolytic stability.     

pH-Responsive Self-assembled Nanoparticles of Simulated P(AA-co-SA)-g-PEG for Drug Release

Simulated graft copolymer of poly(acrylic acid-co-stearyl acylate) [P(AA-co-SA)] and poly(ethylene glycol) (PEG) was synthesized, where acrylic acid, stearyl acylate and PEG was employed as the pH-sensitive, hydrophobic and hydrophilic segment, respectively. Polymeric nanoparticles prepared by the dialysis of simulated graft copolymer solution in dimethylformamide against citrate buffer solution with different pH values were characterized by transmission electron microscopy (TEM), fluorescence technique and laser light scattering (LLS). TEM image revealed the spherical shape of the self-aggregates, which was further confirmed by LLS measurements. The critical aggregation concentration increased markedly (10 to 150 mg/L) with increasing pH (4.6 to 7.0), consistent with the de-protonation of carboxylic groups at higher pH. The hydrodynamic radius of polymeric nanoparticles decreased from 118 nm at pH 3.4 to 90 nm at pH 7.0. The controlled release of indomethacin from those nanoparticles was investigated, and the self-assembled nanoparticles exhibited improved performance in controlled drug release.     

Effect of complexation of poly(acrylic acid) with Cu2+ ions on the size of copper nanoparticles prepared via reduction in aqueous solutions

Sols of zero-valence copper are prepared via the chemical reduction of Cu(II) ions by hydrazine borane in aqueous solutions of high-molecular-mass poly(acrylic acid), which forms stable complexes with copper ions at 20°C in a wide pH range. The study of the composition of coordination centers, the ligand surrounding of metal ions, and the character of distribution of copper ions over poly(acrylic acid) coils in a wide range of solution compositions and pH values shows that the size of copper nanoparticles in the sols can be controlled by varying the ratio between ligand groups (carboxylate anions in poly(acrylic acid)) and copper ions in the reaction system during the synthesis of sols. This effect can be accomplished either by variation in the initial composition of solution or change in pH (the degree of ionization of the initial poly(acrylic acid) in the presence of copper ions).     

Poly(ethylene glycol) micro-patterns as environmentally sensitive template for selective or non-selective adsorption

Poly(ethylene glycol) (PEG), a hydrophilic and repulsive polymer to non-specific adsorption, was stamped onto carboxylic acid-enriched polymer surfaces using the micro-contact printing technique. The patterns are stabilized via hydrogen bonds. Areas printed with PEG were then shown to be non-adsorbed with fluorescein isothiocyanate (FITC)-labeled dextran, while the poly(methacrylic acid) (PMAA) regions could via hydrogen bonding. Due to this contrast, well defined dextran patterns were obtained. Tuned with pH and temperature, the PEG molecules could be detached from the surfaces, erasing the template. Moreover, ionization of PMAA at higher pH induced an abrupt transition to an extended conformation, weakening the interactions between PMAA and dextran. Not only the dextran patterns lose their spatial selectivity, but also the overall adsorption amount is much lower. The pH sensitivity was in a quite narrow range, i.e. around pH 5. As the hydrogen bonds are also temperature sensitive, the attach points of PEG molecules on the surfaces disappeared at higher temperature. For poly(acrylic acid) (PAA) photografted surfaces, the pH sensitivity was more complicated due to the formation of the compact complexes of PEG and PAA molecules.     

Water-soluble hydrogen-bonding interpolymer complex formation between poly(ethylene glycol) and poly(acrylic acid) grafted with poly(2-acrylamido-2-methylpropanesulfonic acid)

Comb-type copolymers of poly(acrylic acid) grafted with poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPSA) side chains form with poly(ethylene glycol), at low pH, water-soluble hydrogen-bonding interpolymer complexes. Turbidimetry, viscometry, and dynamic light scattering measurements suggest that compact, negatively charged, colloidal nanoparticles are formed at pH<3.75. The influence of the structure of the graft copolymers and of the ionic strength of the solution on the size of these nanoparticles was investigated. It was found that their hydrodynamic radius decreases by increasing the molecular mass of the PAMPSA side chains of the graft copolymer and increases with increasing the ionic strength of the solution.     

Poly(acrylic acid)-poly(ethylene glycol) layers on positively charged surface coatings: molecular structure, protein resistance, and application to single protein deposition

A new copolymer (PAA-PEG2000) has been designed, consisting of a negatively charged poly(acrylic acid) (PAA) backbone to which poly(ethylene glycol) (PEG) side chains with a molecular weight of about 2 kDa were grafted in a molecular ratio of 3:10. It readily adsorbs to positively charged surfaces and may be considered to be the anionic counterpart of PEG-grafted poly(l-lysine) (PLL-PEG), which was first described by Kenausis et al. and is widely used to render negatively charged surfaces protein-resistant. The synthesis of PAA-PEG2000 can be carried out in aqueous solution at room temperature and does not require any sophisticated techniques such as handling in an inert gas atmosphere. Using ellipsometry and infrared reflection absorption spectroscopy (IRRAS), the film structure has been carefully analyzed for copolymer adsorption onto three different positively charged surfaces, namely, thin layers of poly(allylamine) (PAH), poly(ethyleneimine) (PEI) and (3-aminopropyl)triethoxysilane (APTES). Besides the film thickness, the conformation of the PEG chains and their orientation with respect to the surface normal appear to be important parameters for the protein resistance of the films. Although PAA-PEG2000 adsorbed to PAH and PEI renders the surfaces inert, only partial protein resistance has been observed if the copolymer is deposited on APTES. In a model application, we have generated heterogeneous surfaces composed of isolated small Au nanoparticles (AuNP's) embedded in a protein-resistant layer of PAA-PEG2000 and demonstrated that the AuNP's can serve as adsorption sites for single protein species. In the future, these nanopatterned surfaces may be used for the investigation of isolated proteins.