Janet L. Burns

Dry powder precursors of cubic liquid crystalline nanoparticles (cubosomes

Cubosomes are dispersed nanostructured particles of cubic phase liquid crystal that have stimulated significant research interest because of their potential for application in controlled-release and drug delivery. Despite the interest, cubosomes can be difficult to fabricate and stabilize with current methods. Most of the current work is limited to liquid phase processes involving high shear dispersion of bulk cubic liquid crystalline material into sub-micron particles, limiting application flexibility. In this work, two types of dry powder cubosome precursors are produced by spray-drying: (1) starch-encapsulated monoolein is produced by spray-drying a dispersion of cubic liquid crystalline particles in an aqueous starch solution and (2) dextran-encapsulated monoolein is produced by spray-drying an emulsion formed by the ethanol–dextran–monoolein–water system. The encapsulants are used to decrease powder cohesion during drying and to act as a soluble colloidal stabilizer upon hydration of the powders. Both powders are shown to form (on average) 0.6 μm colloidally-stable cubosomes upon addition to water. However, the starch powders have a broader particle size distribution than the dextran powders because of the relative ease of spraying emulsions versus dispersions. The developed processes enable the production of nanostructured cubosomes by end-users rather than just specialized researchers and allow tailoring of the surface state of the cubosomes for broader application.

Microstructures formed in a mixed system of a cationic polymer and an anionic surfactant

Microstructures in a mixed solution of sodium dodecyl sulfate (SDS) and the oppositely charged quaternary ammonium-substituted hydroxyethylcellulose polymer JR-400 were imaged by two complementary methods: light microscopy and cryo-transmission electron microscopy. Direct images were taken of the microstructures formed throughout the interaction zones at increasing SDS concentration. In solutions of low SDS concentration, bilayer fragments, small vesicles and disc-like aggregates form. As the SDS concentration is increased and approaches charge neutrality, the solution becomes turbid. Particles imaged by light microscopy and electron microscopy indicate microphase separation with clear flocs of mainly globular structure. No microstructures were observed in the supernatant in the precipitation zone. The precipitate, made of particles of different sizes, was imaged using light microscopy. Further addition of surfactant produced a turbid solution, where electron microscopy images indicated microphase separation with well developed flocs of spherical aggregates. At higher concentrations of SDS, resolubilization took place and a variety of microstructures appeared: vesicles, disc-like and thread-like structures. Upon increased surfactant excess, resolubilization was completed with the formation of spheroidal micelles.

Characterization of the Early Ultrastructural and Biochemical Events Occurring in Dichloromethane Diphosphonate Nephrotoxicity

A chelator, dichloromethane diphosphonate (Cl2MDP), used to treat for malignancy-induced hypercalcemia, has nephrotoxic potential. An acute animal model developed to examine the mechanism was used to further characterize the renal effects. NAG enzymuria appears to be an early premonitor of injury. Ultrastructurally, an increase in size and number of protein-containing phagolysosomal reabsorption droplets in proximal convoluted tubules associated with proteinuria precedes advent of tubular cell necrosis indicating these organelles to be a potential target site for Cl2MDP in the kidney. In vitro studies using rabbit cortical tubules and rat brush border membrane vesicle preparations suggest that the renal toxicity is not due to perturbation of phosphate transport or oxidative metabolism. An operational hypothesis emerges indicating that Cl2MDP may be protein bound affecting carrier protein charge facilitating glomeruler leakage with tubular accumulation via protein transport. Cl2MDP may induce critical cation perturbation at the subcellular level as the mechanism of cell death.

Morphological studies of nanoclusters on grid-supported polymer thin films

Modification of substrates by controlled deposition of nanometer-size particulates ({ital nanoclusters}) is an efficient means of fabricating materials designed for applications in which specific surface interactions play a vital role (e.g., molecular catalysis and microelectronics). We have found that highly dispersed nanoclusters form on thin films of poly(siloxaneimide) (PSI) copolymers supported on copper transmission electron microscopy (TEM) grids when subjected to long anneals at elevated temperatures. In this note, we report on the composition and source of these anomalous nanoclusters, as determined by a variety of electron microscopical techniques. Spectra obtained with parallel electron energy-loss spectroscopy (PEELS) indicate that these particulates, which typically measure 4--18 nm in diameter, are composed of copper with a mean valence of +1. Electron microdiffraction patterns reveal that the nanoclusters are polycrystalline, possessing lattice spacings similar to those of Cu{sub 2}O. Mechanistic routes of formation are suggested based on experimental design, and factors influencing formation are also described.