Growth of textured thin Au coatings on iron oxide nanoparticles with near infrared absorbance.

A homologous series of Au coated iron oxide nanoparticles with hydrodynamic diameters smaller than 60 nm was synthesized with very low Au-to-iron mass ratios, as low as 0.15. The hydrodynamic diameter was determined by dynamic light scattering and the composition by atomic absorption spectroscopy and energy dispersive x-ray spectroscopy. Unusually low Au precursor supersaturation levels were utilized to nucleate and grow Au coatings on iron oxide relative to the formation of pure Au nanoparticles. This approach produced unusually thin coatings by lowering autocatalytic growth of Au on Au, as shown by transmission electron microscopy. Nearly all of the nanoparticles were attracted by a magnet, indicating a minimal number of pure Au particles. The coatings were sufficiently thin to shift the surface plasmon resonance to the near infrared with large extinction coefficients, despite the small particle hydrodynamic diameters observed from dynamic light scattering to be less than 60 nm.

Enhanced pulsed magneto-motive ultrasound imaging using superparamagnetic nanoclusters.

Recently, pulsed magneto-motive ultrasound (pMMUS) imaging augmented with ultra-small magnetic nanoparticles has been introduced as a tool capable of imaging events at molecular and cellular levels. The sensitivity of a pMMUS system depends on several parameters, including the size, geometry and magnetic properties of the nanoparticles. Under the same magnetic field, larger magnetic nanostructures experience a stronger magnetic force and produce larger displacement, thus improving the sensitivity and signal-to-noise ratio (SNR) of pMMUS imaging. Unfortunately, large magnetic iron-oxide nanoparticles are typically ferromagnetic and thus are very difficult to stabilize against colloidal aggregation. In the current study we demonstrate improvement of pMMUS image quality by using large size superparamagnetic nanoclusters characterized by strong magnetization per particle. Water-soluble magnetic nanoclusters of two sizes (15 and 55 nm average size) were synthesized from 3 nm iron precursors in the presence of citrate capping ligand. The size distribution of synthesized nanoclusters and individual nanoparticles was characterized using dynamic light scattering (DLS) analysis and transmission electron microscopy (TEM). Tissue mimicking phantoms containing single nanoparticles and two sizes of nanoclusters were imaged using a custom-built pMMUS imaging system. While the magnetic properties of citrate-coated nanoclusters are identical to those of superparamagnetic nanoparticles, the magneto-motive signal detected from nanoclusters is larger, i.e. the same magnetic field produced larger magnetically induced displacement. Therefore, our study demonstrates that clusters of superparamagnetic nanoparticles result in pMMUS images with higher contrast and SNR.

Synthesis of organic monolayer-stabilized copper nanocrystals in supercritical water.

When water is heated and pressurized above the critical point, it becomes a suitable solvent to employ organic capping ligands to control and stabilize the synthesis of nanocrystals. Without alkanethiol ligands, Cu(NO(3))(2) hydrolyzes to form polydisperse copper(II) oxide particles with diameters from 10 to 35 nm. However, in the presence of 1-hexanethiol, X-ray photoelectron spectroscopy, selected area electron diffraction, and transmission electron microscopy reveal the formation of copper nanocrystals approximately 7 nm in diameter. The use of a different precursor, Cu(CH(3)COO)(2), leads to particles with significantly different morphologies. A mechanism is proposed for sterically stabilized nanocrystal growth in supercritical water that describes competing pathways of hydrolysis to large oxidized copper particles versus ligand exchange and arrested growth by thiols to produce small monodisperse Cu nanoparticles.

Highly luminescent silicon nanocrystals with discrete optical transitions.

A new synthetic method was developed to produce robust, highly crystalline, organic-monolayer passivated silicon (Si) nanocrystals in a supercritical fluid. By thermally degrading the Si precursor, diphenylsilane, in the presence of octanol at 500 degrees C and 345 bar, relatively size-monodisperse sterically stabilized Si nanocrystals ranging from 15 to 40 A in diameter could be obtained in significant quantities. Octanol binds to the Si nanocrystal surface through an alkoxide linkage and provides steric stabilization through the hydrocarbon chain. The absorbance and photoluminescence excitation (PLE) spectra of the nanocrystals exhibit a significant blue shift in optical properties from the bulk band gap energy of 1.2 eV due to quantum confinement effects. The stable Si clusters show efficient blue (15 A) or green (25-40 A) band-edge photoemission with luminescence quantum yields up to 23% at room temperature, and electronic structure characteristic of a predominantly indirect transition, despite the extremely small particle size. The smallest nanocrystals, 15 A in diameter, exhibit discrete optical transitions, characteristic of quantum confinement effects for crystalline nanocrystals with a narrow size distribution.

Catalysis in supercritical CO2 using dendrimer-encapsulated palladium nanoparticles.

Dendrimer-encapsulated nanoparticles are shown to be versatile catalysts for both the hydrogenation of styrene and Heck heterocoupling of iodobenzene and methacrylate in supercritical CO2 (scCO2).

Solution-based particle formation of pharmaceutical powders by supercritical or compressed fluid CO2 and cryogenic spray-freezing technologies.

Micronization is an important procedure used in the pharmaceutical industry to reduce the particle size of active pharmaceutical ingredients (APIs). The spray-drying and milling techniques presently used to micronize drug substances cannot be used to process thermolabile or physically unstable drug substances. Therefore, new micronization techniques, including particle precipitation with supercritical or compressed fluid CO2 and spray-freezing of drug solutions and suspensions into cryogenic gas to produce solid frozen microparticles, are currently being perfected for future use in the pharmaceutical industry. This review highlights the compressed gas and cryogenic liquid technologies being developed as potential solution-based particle formation technologies for drugs that cannot be processed by conventional micronization techniques.

Rapid expansion from supercritical to aqueous solution to produce submicron suspensions of water-insoluble drugs.

Stable suspensions of submicron particles of cyclosporine, a water-insoluble drug, have been produced by rapid expansion from supercritical to aqueous solution (RESAS). To minimize growth of the cyclosporine particles, which would otherwise occur in the free jet expansion, the solution was sprayed into an aqueous Tween-80 (Polysorbate-80) solution. Steric stabilization by the surfactant impedes particle growth and agglomeration. The particles were an order of magnitude smaller than those produced by RESS into air without the surfactant solution. Concentrations as high as 38 mg/mL for 400-700 nm particles were achieved in a 5.0% (w/w) Tween-80 solution.

Encapsulation of lysozyme in a biodegradable polymer by precipitation with a vapor-over-liquid antisolvent.

Lysozyme was encapsulated in biodegradable polymer microspheres which were precipitated from an organic solution by spraying the solution into carbon dioxide. The polymer, either poly(l-lactide) (l-PLA) or poly(DL-lactide-co-glycolide) (PGLA), in dichloromethane solution with suspended lysozyme was sprayed into a CO2 vapor phase through a capillary nozzle to form droplets which solidified after falling into a CO2 liquid phase. By delaying precipitation in the vapor phase, the primary particles became sufficiently large, from 5 to 70 microm, such that they could encapsulate the lysozyme. At an optimal temperature of -20 degrees C, the polymer solution mixed rapidly with CO2, and the precipitated primary particles were sufficiently hard such that agglomeration was markedly reduced compared with higher temperatures. More uniform particles were formed by flowing CO2 at high velocity in a coaxial nozzle to mix the droplets at the CO2 vapor-liquid interface. This process offers a means to produce encapsulated proteins in poly(DL-lactide-co-glycolide) microspheres without earlier limitations of massive polymer agglomeration and limited protein solubility in organic solvents.

Polymeric microspheres prepared by spraying into compressed carbon dioxide.

PURPOSE: The objective was to prepare polymeric microparticles by atomizing organic polymer solutions into a spray chamber containing compressed CO2 (PCA-process) and to study the influence of various process parameters on their morphological characteristics. METHOD: The swelling of various pharmaceutically acceptable polymers [ethyl cellulose, poly(methyl methacrylate), poly(epsilon-caprolactone), poly(dl-lactide), poly(l-lactide) and poly(dl-lactide-glycolide) copolymers] in CO2 was investigated in order to find polymers which did not agglomerate during the spraying process. Poly(l-lactide) (L-PLA) microparticles were prepared by spraying the organic polymer solution into CO2 in a specially designed spraying apparatus. The effect of various process (pressure and temperature of the CO2 phase, flow rate) and formulation (polymer concentration) variables on the morphology and particle size of L-PLA-microparticles was investigated. RESULTS: Polymers with low glass transition temperatures agglomerated even at low temperatures. The formation of microparticles was favored at moderate temperatures, low polymer concentrations, high pressures and high flow rates of CO2. High polymer concentrations and low flow rates resulted in the formation of polymeric fibers. Colloidal L-PLA particles could also be prepared with this technique in a surfactant-free environment. Initial studies on the microencapsulation of drugs resulted in low encapsulation efficiencies. CONCLUSIONS: The PCA method is a promising technique for the preparation of drug-containing microparticles. Potential advantages of this method include the flexibility of preparing microparticles of different size and morphology, the elimination of surfactants, the minimization of residual organic solvents, low to moderate processing temperatures and the potential for scale-up.

Recovery of proteins and amino acids from reverse micelles by dehydration with molecular sieves.

A new method is presented to precipitate proteins and amino acids from reverse micelles by dehydrating the micelles with molecular sieves. Nearly complete precipitation is demonstrated for alpha-chymotrypsin, cytochromec, and trytophan from 2-ethylhexyl sodium sulfosuccinate (AOT)/isooctane/water reverse micelle solutions. The products precipitate as a solid powder, which is relatively free of surfactant. The method does not require any manipulation of pH, ionic strength, temperature, pressure, or solvent composition, and is applicable over a broad range of these properties. This general approach is compared with other techniques. This general approach is compared with other techniques for the recovery of biomolecules from reverse micelles. (c) 1994 John Wiley & Sons, Inc.

Solubilization of biomolecules in carbon dioxide based supercritical fluids.

Supercritical fluid (SF) carbon dioxide offers several advantages compared with organic liquid solvents for separations and reaction processes of thermally labile biomolecules.A major limitation is that the even moderately polar biomolecules are only slightly soluble. Experimental solubility and vapor pressure data were obtained for cholesterol, stigmasterol, and ergosterol in SF CO(2) with and without co-solvents over a pressure range of 100 to 350 bar. Small concentrations of certain co-solvents can increase solubilities of particular sterols by one or two orders of magnitude, but have little effect on other sterols due to complexes formed in the solid phase. The experimental data were correlated using component solubility parameters to obtain the unlike-pair attraction constant used in a modified van der Waals equation of state.