Though gold nanoparticles have been considered bio-inert, recent studies have questioned their safety. To reduce the potential for toxicity, we developed a nanoclustering of gold and iron oxide as a nanoparticle (nanorose) which biodegrades into subunits to facilitate rapid excretion. In this present study, we demonstrate acid and macrophage lysosomal degradation of nanorose via loss of the near-infrared optical shift, and clearance of the nanorose in vivo following i.v. administration in C57BL/6 mice by showing gold concentration is significantly reduced in 11 murine tissues in as little as 31 days (P < 0.01). Hematology and chemistry show no toxicity of nanorose injected mice up to 14 days after administration. We conclude that the clustering design of nanorose does enhance the excretion of these nanoparticles, and that this could be a viable strategy to limit the potential toxicity of gold nanoparticles for clinical applications. From the Clinical Editor: The potential toxicity of nanomaterials is a critically important limiting factor in their more widespread clinical application. Gold nanoparticles have been classically considered bio-inert, but recent studies have questioned their safety. The authors of this study have developed a clustering gold and iron oxide nanoparticle (nanorose), which biodegrades into subunits to facilitate rapid excretion, resulting in reduced toxicity. Published by Elsevier Inc.
Freezing of protein solutions perturbs protein conformation, potentially leading to aggregate formation during long-term storage in the frozen state. Macroscopic protein concentration profiles in small cylindrical vessels were determined for a monoclonal antibody frozen in a trehalose-based formulation for various freezing protocols. Slow cooling rates led to concentration differences between outer edges of the tank and the center, up to twice the initial concentration. Fast cooling rates resulted in much smaller differences in protein distribution, likely due to the formation of dendritic ice, which traps solutes in micropockets, limiting their transport by convection and diffusion. Analysis of protein stability after more than 6 months storage at either 10 degrees C or 20 degrees C [above glass transition temperature (Tg)] or 80 degrees C (below Tg) revealed that aggregation correlated with the cooling rate. Slow-cooled vessels stored above Tg exhibited increased aggregation with time. In contrast, fast-cooled vessels and those stored below Tg showed small to no increase in aggregation at any position. Rapid entrapment of protein in a solute matrix by fast freezing results in improved stability even when stored above Tg. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:11941208, 2013
Foams used for mobility control in CO2 flooding, and for more secure sequestration of anthropogenic CO2, can be stabilized with nanoparticles, instead of surfactants, bringing some important advantages. The solid nature of the nanoparticles in stabilized foams allows them to withstand the high-temperature reservoir conditions for extended periods of time. They also have more robust stability because of the large adsorption energy required to bring the nanoparticles to the bubble interface.
Silica nanoparticle-stabilized CO2-in-brine foams were generated by the co-injection of CO2 and aqueous nanoparticle dispersion through beadpacks, and through unfractured and fractured sandstone cores. Foam flow in rock matrix and fracture, both through Boise and Berea sandstones, was investigated. The apparent viscosity measured from foam flow in various porous media was also compared with that measured in a capillary tube, installed downstream of beadpacks and cores.
The domain of foam stability and the apparent foam viscosity in beadpacks was first investigated with focus on how the surface wettability of nanoparticles affects the foam generation. A variety of silica nanoparticles without any surface coating and with different coatings were tested, and the concept of hydrophilic/CO2-philic balance (HCB) was found to be very useful in designing surface coatings that provide foams with robust stability. Opaque, white CO2-in-water foams (bubble diameter < 100 µm) were generated with either polyethyleneglycol-coated silica or methylsilyl-modified silica nanoparticles with CO2 densities between 0.2 and 0.9 g/cc. The synergistic interactions at the surface of nanoparticles (bare colloidal silica) and surfactant (caprylamidopropyl betaine) in generating stable CO2 foams were also investigated.
The common and distinct requirements to generate stable CO2 foams with 5-nm silica nanoparticles, in rock matrices and in fractures, were characterized by running foam generation experiments in Boise and Berea sandstone cores. The threshold shear rates for foam generation in matrix and in fracture, both in Boise and Berea sandstones, were characterized. The ability of nanoparticles to generate foams only above a threshold shear rate is advantageous, because high shear rates are associated with high permeability zones and fractures. Reducing CO2 mobility in these zones with foam diverts CO2 into lower permeability regions that still contain unswept oil.
Perovskite catalysts are of great interest as replacements for precious metals and oxides used in the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). Perovskite electrocatalysts have been shown to have greater specific activities than precious metals and their oxides, but high mass activities have not yet been realized due to vague or incomplete mechanistic understanding of catalysts active sites coupled with inadequate synthesis techniques which often result in unwanted phase impurities and micron-scale materials. Herein, we demonstrated precise control over the synthesis of essentially phase pure perovskite nanocrystals with mass activities exceeding that of IrO2 and possessing comparable or greater bifunctional character than leading precious metals such as Ir and Pt. The robust aqueous synthesis of ABO3 perovskites such as LaCoO3, LaMnO3, LaNixFe1-xO3 and Ba0.5Sr0.5Co0.8Fe0.2O3-δ will be demonstrated, and the resulting electrocatalytic activities of these materials will be presented. We will examine these results in the context of proposed perovskite activity descriptors, surface hydroxylation, oxygen vacancies and mechanistic pathways for the OER and ORR. Catalytic activity is determined using electroanalytical techniques such as rotating disk electrochemistry and cyclic voltammetry in conjunction with materials characterization enabled by dynamic light scattering, electron microscopy, nitrogen sorption, X-ray photoelectron spectroscopy and X-ray diffraction. It is demonstrated that these highly active perovskite catalysts are an emerging replacement for the precious metals used not just for the OER and ORR, but also for the chlor-alkali and oxygen depolarized cathode industries as well.
Metal oxides have gained significant interest aspseudocapacitor electrodes due to reversible faradaicsurface reactions that allow for high power density andgreater energy storage than carbon based electric doublelayer capacitors. However, classically investigatedmaterials like RuO2, MnO2, and Ni(OH)2 suffer from highcost, low life cycles, or limited potential windows,respectively.1-3 As such, there is growing demand for newmaterials with improved energy storage and stability.Herein, we demonstrate the capacitive characteristics ofthree lanthanum based perovskite type oxides, LaMnO3,LaNiO3, and LaCoO3. Based on the inherent nature ofperovskites to contain oxygen vacancies, we demonstratethrough cyclic voltammetry that perovskites store chargethrough anions in alkaline electrolytes, likely in the formof hydroxides. This hypothesis was tested by inducingextrinsic oxygen vacancies in LaMnO3 through a lowtemperature reduction in H2/Ar. It was found thatsubstoichiometric LaMnO3-δ exhibits ~20% greatercapacitance, highlighting the significance of oxygenvacancies as charge-storage sites in these perovskite typeoxides. Importantly, due to the well-known oxide andproton ionic conduction characteristics of perovskites, wedemonstrate that charge storage is not limited to thesurface of these materials. Rather, it may extend into thebulk of the structure, leading to higher energy storagethan traditional psuedocapacitors which are inherentlylimited by surface confined reactions. As the first study ofthese materials for pseudocapacitor applications, onlymoderate structural and electrochemical optimizationshave been carried out. As such, the high specificcapacitances of >500F/g and high cycling stability for thematerials of this study imply a promising future forperovskite structured pseudocapacitors.
A magnetic nanoparticle suitable for imaging a geological structure having one or more magnetic metal or metal oxide nanoparticles with a polymer grafted to the surface to form a magnetic nanoparticle, wherein the magnetic nanoparticle displays a colloidal stability under harsh salinity conditions or in a standard API brine.
A method for preparing poorly water soluble drug particles is disclosed. The method comprises dissolving a drug in at least one organic solvent to form a drug/organic mixture, spraying the drug/organic mixture into an aqueous solution and concurrently evaporating the organic solvent in the presence of the aqueous solution to form an aqueous dispersion of the drug particles. The resulting drug particles are in the nanometer to micrometer size range and show enhanced dissolution rates and reduced crystallinity when compared to the unprocessed drug. The present invention additionally contemplates products and processes for new drug formulations of insoluble drug particles having high dissolution rates and extremely high drug-to-excipient ratios
Solutions of therapeutic proteins often gel and become too viscous to deliver via subcutaneous injection at high protein concentrations (>200 mg ml(-1)). Herein, we demonstrate that protein molecules can be crowded into colloidally stable dispersions of distinct nanoclusters that exhibit equilibrium hydrodynamic diameters without gelation at very high concentrations (up to 320 mg ml(-1)). The nanoclusters form spontaneously upon concentration of protein solutions in the presence of a crowding agent, for example trehalose. Remarkably nanoclusters of the same size are produced by dilution of protein powder in buffer. Nanocluster size is stable for extended time periods, and upon frozen storage and thawing. Thus, the nanocluster diameter appears to be governed by equilibrium behavior arising from a balance of short and long-ranged monomer-monomer, monomer-cluster and cluster-cluster interactions, as calculated by a free energy model.
Monoclonal antibodies continue to command a large market for treatment of a variety of diseases. In many cases, the doses required for therapeutic efficacy are large, limiting options for antibody delivery and administration. We report a novel formulation strategy based on dispersions of antibody nanoclusters that allows for subcutaneous injection of highly concentrated antibody (similar to 190?mg/mL). A solution of monoclonal antibody 1B7 was rapidly frozen and lyophilized using a novel spiral-wound in-situ freezing technology to generate amorphous particles. Upon gentle stirring, a translucent dispersion of approximately 430?nm protein clusters with low apparent viscosity (similar to 24?cp) formed rapidly in buffer containing the pharmaceutically acceptable crowding agents such as trehalose, polyethylene glycol, and n-methyl-2-pyrrolidone. Upon in vitro dilution of the dispersion, the nanoclusters rapidly reverted to monomeric protein with full activity, as monitored by dynamic light scattering and antigen binding. When administered to mice as an intravenous solution, subcutaneous solution, or subcutaneous dispersion at similar (4.67.3?mg/kg) or ultra-high dosages (51.6?mg/kg), the distribution and elimination kinetics were within error and the protein retained full activity. Overall, this method of generating high-concentration, low-viscosity dispersions of antibody nanoclusters could lead to improved administration and patient compliance, providing new opportunities for the biotechnology industry. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:37633778, 2012
Achieving synergy between inexpensive metals and metal oxides is a key challenge for the development of highly active, economical catalysts. We report the synthesis and characterization of a highly active oxygen reduction reaction(ORR) catalyst composed of Ag particles (3 nm) in intimate contact with thin (similar to 1 nm) MnOx domains on Vulcan carbon (VC) as shown via electron microscopy. A new electroless co-deposition scheme, whereby MnO4- ions are reduced by carbon, formed nanosized MnOx reduction centers for Ag nanoparticle deposition. A bifunctional mechanism for ORR is proposed, in which the HO2- intermediate is formed electrochemically and is regenerated via disproportionation into OH- and O-2. A 3x mass activity enhancement is observed for Ag-MnOx/VC (125 mA/mg(Ag+MnOx)) over the linear combination of pure component activities using rotating disk voltammetry. The Ag-MnOx/VC mass activity is comparable to commercial Pd/VC (111 inA/rng(Pd)) and Pt/VC (136 mA/mg(Pt)). Furthermore, the number of electrons transferred for ORR reaches 3.5 for Ag-MnOx, higher than for MnOx (2.8) and close to the full four-electron ORR. The synergy can be rationalized by ensemble effects, where Ag and MnOx domains facilitate the formation and disproportionation of HO2-, respectively, and ligand effects from the unique electronic interaction at the Ag-MnOx interface.
The preparation of gold nanoparticles incorporated in self-assembled and ordered semifluorinated poly(ethylene oxide)-b-poly(1H,1H-dihydroperfluorooctyl methacrylate) (PEO-b-PFOMA) thin films was explored through annealing induced phase transition. The micellar thin films containing gold nanoparticles whose average size was dependent on the block length of the copolymer were produced by spin casting the solution of PEO10k-b-PFOMA(12k) and PEO20k-b-PFOMA(22k) in chloroform with a gold precursor, LiAuCl4. Three annealing modes were attempted for the Au-loaded micellar films: solvent vapor annealing, supercritical CO2 at 70 degrees C and thermal annealing at 100 degrees C. The nanoparticles dispersed in PEO regions were forced to follow the morphological change of the PEO phase and grew into larger single particles in PEO domains. The solvent annealing produced higher ordering of Au nanoparticles than scCO(2) or thermal annealing. (C) 2012 Elsevier B.V. All rights reserved.
Rapid flocculation of nanoparticle dispersions of a poorly water soluble drug, itraconazole (Itz), was utilized to produce amorphous powders with desirable dissolution properties for high bioavailability in rats. Antisolvent precipitation (AP) was utilized to form Itz nanodispersions with high drug loadings stabilized with hydroxypropylmethylcellulose (HPMC) or the pH-sensitive Eudragit (R) L100-55 (EL10055). The HPMC dispersions were flocculated by desolvating the polymer through the addition of a divalent salt, and the enteric EL10055 by reducing the pH. The formation of open flocs by diffusion limited aggregation facilitated redispersion of the flocs at pH 6.8. Upon redispersion of the flocculated nanoparticles at pH 6.8, the particle size was modestly larger than the original size, on the order of 1 mu m. High in vitro supersaturation (AUC) of the flocculated nanoparticle dispersions was observed in micellar media at pH 6.8, after 2 hours initial exposure at pH 1.2 to simulate the stomach, relative to the AUC for a commercially available Itz formulation, Sporanox. Greater in vivo bioavailability in rats was correlated directly to the higher in vitro AUC at pH 6.8 with micelles during the pH shift experiment for the flocculated nanoparticle dispersions relative to Sporanox. The ability to generate and sustain high supersaturation in micellar media at pH 6.8, as shown with the in vitro pH shift dissolution test, is beneficial for increasing bioavailability of Itz by oral delivery.
Interfacial interactions between sub-4 nm metal alloy nanoparticles and carbon supports, although not well understood at the atomic level, may be expected to have a profound influence on catalytic properties. Pd3Pt2 alloy particles comprised of a disordered surface layer over a corrugated crystalline core are shown to exhibit strong interfacial interactions with a similar to 20-50 nm spherical carbon support, as characterized by probe aberration corrected scanning transmission electron microscopy (pcSTEM). The disordered shells were formed from defects introduced by Pd during arrested growth synthesis of the alloy nanoparticles. The chemical and morphological changes in the catalyst, before and after cyclic stability testing (1000 cycles, 0.5-1.2V). were probed with cyclic voltammetry (CV), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and pcSTEM. The strong metal-support interaction, along with the uniform alloy structure raised the mass activity by a factor of 1.8 versus pure Pt. The metal-support interactions also mitigated nanoparticle coalescence, dissolution, and ripening, resulting in only a 20% loss in mass activity (versus 60% for pure Pt on carbon) after the cyclic stability test. The design of alloy structure, guided by insight from atomic scale pcSTEM, for enhanced catalytic activity and stability, resulting from strong wetting with a deformable disordered shell, has the potential to be a general paradigm for improving catalytic performance. (C) 2011 Elsevier Ltd. All rights reserved.
The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P < 0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P < 0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.3.036009]
A series of sub-100 nm superparamagnetic iron oxide nanoparticles with amphiphilic poly(acrylic acid-b-butylacrylate); PAA-b-PBA) copolymer shells were synthesized and characterized by NMR spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), thermogravimetric analysis (TGA), and a superconducting quantum interference device (SQUID) to investigate the effect of the polymer structure on the interfacial tension for nanoparticles adsorbed at the dodecane-water interface. Large reductions in interfacial tension of up to 27.6 mN/m were measured at nanoparticle concentrations of 0.27 wt %, indicating significant nanoparticle adsorption and interaction between the oil and water molecules at the interface. The adsorption energy of the polymer-coated nanoparticles at the dodecane/water interface was determined from the interfacial tension and nanoparticle radius, and analyzed in terms of the structure of the polymer stabilizer. Furthermore, the equilibrium adsorption of amphiphilic copolymer-functionalized iron oxide nanoclusters at the oil water interface was determined by material balance from the concentration in the excess water phase and the known overall oil/water interfacial area. The formation and stabilization of oil droplets were on the order of 10 mu m in water with unusually low nanoparticle concentrations was explained in terms of the high interfacial activity of the particles.
The ability to design and characterize uniform, bimetallic alloy nanoparticles, where the less active metal enhances the activity of the more active metal, would be of broad interest in catalysis. Herein, we demonstrate that simultaneous reduction of Ag and Pd precursors provides uniform, Ag-rich AgPd alloy nanoparticles (similar to 5 nm) with high activities for the oxygen reduction reaction (ORR) in alkaline media. The particles are crystalline and uniformly alloyed, as shown by X-ray diffraction and probe corrected scanning transmission electron microscopy. The ORR mass activity per total metal was 60% higher for the AgPd2 alloy relative to pure Pd. The mass activities were 2.7 and 3.2 times higher for Ag9Pd (340 mA/mg(metal)) and Ag4Pd (598 mA/mg(metal)), respectively, than those expected for a linear combination of mass activities of Ag (60 mA/mg(Ag)) and Pd (799 mA/mg(Pd)) particles, based on rotating disk voltammetry. Moreover, these synergy factors reached 5-fold on a Pd mass basis. For silver-rich alloys (Ag <= 4Pd), the particle surface is shown to contain single Pd atoms surrounded by Ag from cyclic voltammetry and CO stripping measurements. This morphology is favorable for the high activity through a combination of modified electronic structure, as shown by XPS, and ensemble effects, which facilitate the steps of oxygen bond breaking and desorption for the ORR. This concept of tuning the heteroatomic interactions on the surface of small nanoparticles with low concentrations of precious metals for high synergy in catalytic activity may be expected to be applicable to a wide variety of nanoalloys.
Background and Objectives The macrophage is an important early cellular marker related to risk of future rupture of atherosclerotic plaques. Two-channel two-photon luminescence (TPL) microscopy combined with optical coherence tomography (OCT) was used to detect, and further characterize the distribution of aorta-based macrophages using plasmonic gold nanorose as an imaging contrast agent. Study Design/Materials and Methods: Nanorose uptake by macrophages was identified by TPL microscopy in macrophage cell culture. Ex vivo aorta segments (8 x 8 x 2 mm(3)) rich in macrophages from a rabbit model of aorta inflammation were imaged by TPL microscopy in combination with OCT. Aorta histological sections (5 mm in thickness) were also imaged by TPL microscopy. Results: Merged two-channel TPL images showed the lateral and depth distribution of nanorose-loaded macrophages (confirmed by RAM-11 stain) and other aorta components (e.g., elastin fiber and lipid droplet), suggesting that nanorose-loaded macrophages are diffusively distributed and mostly detected superficially within 20 mm from the luminal surface of the aorta. Moreover, OCT images depicted detailed surface structure of the diseased aorta. Conclusions: Results suggest that TPL microscopy combined with OCT can simultaneously reveal macrophage distribution with respect to aorta surface structure, which has the potential to detect vulnerable plaques and monitor plaque-based macrophages overtime during cardiovascular interventions. Lasers Surg. Med. 44:49-59, 2012. (C) 2012 Wiley Periodicals, Inc.
Paramagnetic nanoparticles are potentially useful for monitoring of immiscible fluids distribution in subsurface, as they can be induced to move by an imposed magnetic field. The nanoparticles can be designed to be preferentially adsorbed at oil-water interface, as well as to have the long-term dispersion stability with minimal retention in the porous medium to be monitored. When exposed to magnetic field, they generate sufficient interfacial movements for external detection. When paramagnetic nanoparticles are either adsorbed at oil-water or air-water interface or dispersed in one of two fluid phases co-existing in pores, and exposed to external magnetic field, the resultant particle movements displace the interface. Interfacial tension acts as a restoring force, leading to interfacial fluctuation and a pressure (sound) wave. Our previous work (Prodanovic et al., 2010) provided a theoretical explanation for the motion of the interface between a suspension of paramagnetic nanorods and a non-magnetized fluid in a cylindrical dish, as measured by phase-sensitive optical coherence tomography (PS-OCT). Here we report on additional experiments carried out with a range of in-house synthesized and surface-modified iron-oxide nanoparticles. We also improved numerical method to be volume conserving for more quantitative matching. The measurements of interfacial motion by PS-OCT reported confirm theoretical predictions of the frequency doubling and the importance of material properties, such as magnetic susceptibility, for the interface displacement. The results are encouraging: this laboratory and modeling study is thus an important step to develop a magnetic field-based method for an accurate, non-invasive determination of multiphase fluids distribution in reservoir rock. With the combined experimental and modeling work, strategies for improved nanoparticle design will be developed so that the interfacial, thereby acoustic, response can be magnified. (C) 2011 Elsevier B.V. All rights reserved.