Aliskiren-based therapy was well tolerated and produced sustained blood pressure reductions in patients with hypertension over 6 months, greater than those with ramipril-based therapy.

Unambiguous and selective standoff (non-contact) infield detection of nitro-containing explosives and taggants is an important goal but difficult to achieve with standard analytical techniques. Oxidative fluorescence quenching is emerging as a high sensitivity method for detecting such materials but is prone to false positives—everyday items such as perfumes elicit similar responses. Here we report thin films of light-emitting dendrimers that detect vapours of explosives and taggants selectively—fluorescence quenching is not observed for a range of common interferents. Using a combination of neutron reflectometry, quartz crystal microbalance and photophysical measurements we show that the origin of the selectivity is primarily electronic and not the diffusion kinetics of the analyte or its distribution in the film. The results are a major advance in the development of sensing materials for the standoff detection of nitro-based explosive vapours, and deliver significant insights into the physical processes that govern the sensing efficacy.

Cronobacter sakazakii is an opportunistic foodborne pathogen that can infect newborns through powdered infant formula (PIF). In this study, we developed a novel enhanced lateral flow immunoassay (LFA) with enhanced sensitivity for detection of C. sakazakii in PIF by the naked eye. The proposed strategy for signal enhancement of the traditional LFA used concentrated gold nanoparticles (AuNP) as the enhancer to conjugate with capture antibodies, which could increase the immobilized capture antibodies concentration at the detection zone to improve capture efficiency. Besides, the detection signal was further amplified by accumulated AuNP as the C. sakazakii labeled with AuNP probes was captured by antibodies conjugated with enhancer at the test line. We also studied the effect of different concentrations of capture antibodies and concentrated AuNP on detection performance, and found that 2.2 mg/mL of capture antibodies and 0.06 nM concentrated AuNP were the optimal combination that could avoid a false-positive signal and maximally amplify the detection signal of the enhanced LFA. Using this strategy, the detection sensitivity of the enhanced LFA was 10 cfu/mL and improved 100-fold compared with traditional LFA. The strip was highly specific to C. sakazakii, and the time for detection of C. sakazakii in PIF was shortened by 3 h. In summary, the enhanced LFA developed by the addition of concentrated AuNP as the enhancer can be used as a sensitive, rapid, visual qualitative and point-of-care test method for detecting target analytes.

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Abstract:Fluorescence-based sensing with organic semiconductors is a powerful method for the detection of a broad range of analytes including explosives, chemical weapons and drugs.Diffusion of an analyte into an organic semiconductor thin film, and its subsequent interaction with the chromophore are key factors that govern the sensing performance of a chemosensor.In this study the diffusion behaviour of an explosive analyte analogue into a sensing film of a conjugated dendrimer was investigated using a quartz crystal microbalance (QCM) and correlated with neutron reflectivity measurements. The mechanistic insights of paranitrotoluene (pNT) sorption in the films of different thicknesses of a first generation dendrimer with fluorenyl surface groups, carbazole dendrons and a spirobifluorene core were studied and interpreted in terms of the underlying kinetics and thermodynamics. Sorption measurements suggest that the process of diffusion of pNT vapour into the dendrimer films is Super Case II, which involves swelling of the film. Swelling of the film was confirmed by neutron reflectometry measurements, which also showed uniform distribution of the pNT molecules throughout the entire film thickness. The activation energy barrier and change in Gibbs free energy in the sorption process were calculated from the QCM responses. The sorption process was found to be thermodynamically (not kinetically) controlled and independent of film thickness. This work sheds insight into the structure-property relationships that govern the performance of organic semiconductor fluorescence-based chemosensors.

Monoolein cubosomes containing either spironolactone (SPI) or nifedipine (NI) were prepared using a high-pressure homogenization technique and characterized in terms of their solubility and oral bioavailability. The mean particle size, polydispersity index (PDI), zeta potential, solubility and encapsulation efficiency (EE) values of the SPI-and NI-loaded cubosomes were determined to be 90.4 nm, 0.187, 13.4 mV, 163 µg/mL and 90.2%, and 91.3 nm, 0.168, 12.8 mV, 189 µg/mL and 93.0%, respectively, which were almost identical to those of the blank cubosome. Small-angle X-ray scattering analyses confirmed that the SPI-loaded, NIloaded and blank cubosomes existed in the cubic space group Im3 m. The lattice parameters of the SPI-and NI-loaded cubosomes were 147.6 and 151.6 Å, respectively, making them almost identical to that of blank cubosome (151.0 Å). The in vitro release profiles of the SPI-and NI-loaded cubosomes showed that they released less than 5% of the drugs into various media over 12-48 h, indicating that most of the drug remained encapsulated within the cubic phase of their lipid bilayer. Furthermore, the in vivo pharmacokinetic results suggested that these cubosomes led to a considerable increase in the systemic oral bioavailability of the drugs compared with pure dispersions of the same materials. Notably, the stability results indicated that the mean particle size and PDI values of these cubosomes were stable for at least 4 weeks. Taken together, these results demonstrate that monoolein cubosomes represent promising drug carriers for enhancing the solubility and oral bioavailability of poorly water-soluble drugs.Key words cubosome; drug carrier; monoolein; nifedipine; spironolactone; high-pressure homogenizationThe low oral bioavailability of poorly water-soluble drugs remains one of the most challenging aspects of drug development. A wide variety of formulation approaches, including lipid nanoparticles, solid dispersions, complexes with cyclodextrin or chitosan-alginates, nanoemulsions and liposomes, have been used to enhance the solubility and bioavailability of several poorly water-soluble drugs. [1][2][3][4][5] Cubosomes have recently attracted considerable interest from formulation scientists in terms of their potential application as drug delivery systems based on their highly ordered, compartmentalized internal structures, high lipid content and large surface area.Cubosomes are inverse bicontinuous cubic lyotropic crystalline nanoparticles that can be loaded with poorly water-soluble drugs in their three-dimensional cubic phases, leading to pronounced increases in the solubility, stability and bioavailability of these drugs.6-9) Cubosomes can be prepared using nontoxic, biocompatible and biodegradable ingredients, and can be readily used to encapsulate lipophilic drugs. Monoolein is a common amphiphilic building block for the preparation of cubosomes, 10) and is relatively cheap compared with other commonly used lipid excipients such as phytantriol. Nonionic triblock copolymer (Pluronic F-127) is ...

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The diffusion of p-nitrotoluene vapours into polymer or dendrimer sensing films follows Super Case II dynamics in which the quenching efficiency is strongly correlated to an accelerating analyte front propagating through the neat film rather than being reliant on exciton diffusion.