James Long

Formation and enhanced biocidal activity of water-dispersable organic nanoparticles

Water-insoluble organic compounds are often used in aqueous environments in various pharmaceutical and consumer products. To overcome insolubility, the particles are dispersed in a medium during product formation, but large particles that are formed may affect product performance and safety. Many techniques have been used to produce nanodispersions-dispersions with nanometre-scale dimensions-that have properties similar to solutions. However, making nanodispersions requires complex processing, and it is difficult to achieve stability over long periods. Here we report a generic method for producing organic nanoparticles with a combination of modified emulsion-templating and freeze-drying. The dry powder composites formed using this method are highly porous, stable and form nanodispersions upon simple addition of water. Aqueous nanodispersions of Triclosan (a commercial antimicrobial agent) produced with this approach show greater activity than organic/aqueous solutions of Triclosan.

Size and shape control for water-soluble magnetic cobalt nanoparticles using polymer ligands

We report a synthesis of monodisperse water-soluble magnetic Co nanoparticles using a facile reduction method in aqueous media in the presence of alkyl thioether end-functionalized poly(methacrylic acid) (PMAA-DDT) ligands. The size and shape of the nanoparticles are both tunable by varying synthesis conditions. The size of the spherical nanoparticles can be tuned between 2–7.5 nm by changing the concentration of the polymer. Our synthesis approach also provides a route for producing much larger spherical nanoparticles of 80 nm as well as anisotropic nanorods of 15 × 36 nm. The spherical nanoparticles are superparamagnetic at room temperature. The nanoparticles can be stable in water for up to eight weeks when 0.12 mM PMAA-DTT with molecular weight of 13500 g mol−1 is used as ligand.

Antiretroviral solid drug nanoparticles with enhanced oral bioavailability: production, characterization, and in vitro-in vivo correlation.

Nanomedicine strategies have produced many commercial products. However, no orally dosed HIV nanomedicines are available clinically to patients. Although nanosuspensions of drug particles have demonstrated many benefits, experimentally achieving >25 wt% of drug relative to stabilizers is highly challenging. In this study, the emulsion-templated freeze-drying technique for nanoparticles formation is applied for the first time to optimize a nanodispersion of the leading non-nucleoside reverse transcriptase inhibitor efavirenz, using clinically acceptable polymers and surfactants. Dry monoliths containing solid drug nanoparticles with extremely high drug loading (70 wt% relative to polymer and surfactant stabilizers) are stable for several months and reconstitute in aqueous media to provide nanodispersions with z-average diameters of 300 nm. The solid drug nanoparticles exhibit reduced cytoxicity and increased in vitro transport through model gut epithelium. In vivo studies confirm bioavailability benefits with an approximately four-fold higher pharmacokinetic exposure after oral administration to rodents, and predictive modeling suggests dose reduction with the new formulation may be possible.

Facile synthesis of stable, water-soluble magnetic CoPt hollow nanostructures assisted by multi-thiol ligands

We report the synthesis of CoPt hollow nanostructures using a simple reduction method in aqueous solution in the presence of poly(methacrylic acid) pentaerythritol tetrakis (3-mercaptopropionate) (PMAA-PTMP) polymer or a mixture of O-[2-(3-mercaptopropionyl-amino)ethyl]-O′-methylpolyethylene glycol (PEG-SH) polymer and cysteine-cysteine-alanine-leucine-asparagine-asparagine (CCALNN) peptide ligands. The presence of the multi-thiol functional group of the ligands is essential for the formation of the hollow nanostructures and their perimeter size can be tuned within the range of 7–54 nm by changing peptide concentration or length of polymer. These hollow nanostructures are water-soluble and superparamagnetic at room temperature. They are stable in a wide range of pH from 1 to 10, high electrolyte concentration up to 2 M NaCl, and in cell culture medium which makes them have great potential to be utilised in biomedical applications.

Synthetic microarray data generation with RANGE and NEMO

MOTIVATION For testing and sensitivity analysis purposes, it is beneficial to have known transcription networks of sufficient size and variability during development of microarray data and network deconvolution algorithms. Description of such networks in a simple language translatable to Systems Biology Markup Language would allow generation of model data for the networks. RESULTS Described herein is software (RANGE: RAndom Network GEnerator) to generate large random transcription networks in the NEMO (NEtwork MOtif) language. NEMO is recognized by a grammar for transcription network motifs using lex and yacc to output Systems Biology Markup Language models for either specified or randomized gene input functions. These models of known networks may be input to a biochemical simulator, allowing the generation of synthetic microarray data. AVAILABILITY http://range.sourceforge.net

Comprehensive study of DNA binding on iron (II,III) oxide nanoparticles with a positively charged polyamine three-dimensional coating.

Iron (II,III) oxide Fe3O4 nanoparticles (25 and 50 nm NPs) are grafted with amine groups through silanization in order to generate a positively charged coating for binding negatively charged species including DNA molecules. The spatial nature of the coating changes from a 2-D-functionalized surface (monoamines) through a layer of amine oligomers (diethylenetriamine or DETA, about 1 nm in length) to a 3-D layer of polyamine (polyethyleneimine or PEI, thickness ≥3.5 nm). These Fe3O4-PEI NPs were prepared by binding short-chain PEI polymers to the iodopropyl groups grafted on the NP surface. In this work, the surface charge density, or zeta potential, of the nanoparticles is found not to be the only factor influencing the DNA binding capacity, which also seems not to be affected by their buffering capacity profile in the range of pH 4-10. This study also allows the investigation of this 3-D effect on the surface of a nanoparticle as opposed to conventional 2-D amine functionalization. The flexibility of the PEI coating, which consists of only 1, 2, and 3° amines, on the nanoparticle surface has a significant influence on the overall DNA binding capacity and the binding efficiency (or N/P ratio). These polyamine-functionalized nanoparticles can be used in the purification of biomolecules and the delivery of drugs and large biomolecules.

ODES: an overlapping dense sub-graph algorithm

SUMMARY Enumeration of the dense sub-graphs of a graph is of interest in community discovery and membership problems, including dense sub-graphs that overlap each other. Described herein is ODES (Overlapping DEnse Sub-graphs), pthreads parallelized software to extract all overlapping maximal sub-graphs whose densities are greater than or equal to a specified cutoff density of at least 1/2. AVAILABILITY AND IMPLEMENTATION http://dense.sf.net