Real-Time Observation of "Soft" Magic-Size Clusters during Hydrolysis of the Model Metallodrug Bismuth Disalicylate.

Colloidal bismuth therapeutics have been used for hundreds of years, yet remain mysterious. Here we report an X-ray pair distribution function (PDF) study of the solvolysis of bismuth disalicylate, a model for the metallodrug bismuth subsalicylate (Pepto-Bismol). This reveals catalysis by traces of water, followed by multistep cluster growth. The ratio of the two major species, {Bi9O7} and {Bi38O44}, depends on exposure to air, time, and the solvent. The solution-phase cluster structures are of significantly higher symmetry in comparison to solid-state analogues, with reduced off-center Bi3+ displacements. This explains why such "magic-size" clusters can be both stable enough to crystallize and sufficiently labile for further growth.

Polysaccharide Chain Length of Lipopolysaccharides From Salmonella Minnesota Is a Determinant of Aggregate Stability, Plasma Residence Time and Proinflammatory Propensity in vivo.

Lipopolysaccharides (LPS) originate from the outer membrane of Gram-negative bacteria and trigger an inflammatory response via the innate immune system. LPS consist of a lipid A moiety directly responsible for the stimulation of the proinflammatory cascade and a polysaccharide chain of variable length. LPS form aggregates of variable size and structure in aqueous media, and the aggregation/disaggregation propensity of LPS is known as a key determinant of their biological activity. The aim of the present study was to determine to which extent the length of the polysaccharide chain can affect the nature of LPS structures, their pharmacokinetics, and eventually their proinflammatory properties in vivo. LPS variants of Salmonella Minnesota with identical lipid A but with different polysaccharide moieties were used. The physical properties of LPS aggregates were analyzed by zetametry, dynamic light scattering, and microscopy. The stability of LPS aggregates was tested in the presence of plasma, whole blood, and cultured cell lines. LPS pharmacokinetics was performed in wild-type mice. The accumulation in plasma of rough LPS (R-LPS) with a short polysaccharidic chain was lower, and its hepatic uptake was faster as compared to smooth LPS (S-LPS) with a long polysaccharidic chain. The inflammatory response was weaker with R-LPS than with S-LPS. As compared to S-LPS, R-LPS formed larger aggregates, with a higher hydrophobicity index, a more negative zeta potential, and a higher critical aggregation concentration. The lower stability of R-LPS aggregates could be illustrated in vitro by a higher extent of association of LPS to plasma lipoproteins, faster binding to blood cells, and increased uptake by macrophages and hepatocytes, compared to S-LPS. Our data indicate that a long polysaccharide chain is associated with the formation of more stable aggregates with extended residence time in plasma and higher inflammatory potential. These results show that polysaccharide chain length, and overall aggregability of LPS might be helpful to predict the proinflammatory effect that can be expected in experimental settings using LPS preparations. In addition, better knowledge and control of LPS aggregation and disaggregation might lead to new strategies to enhance LPS detoxification in septic patients.

Microchip Random Laser based on a disordered TiO2-nanomembranes arrangement.

We developed a new scheme for obtaining coherent random lasing based on a chip consisting of a polymer film doped with Rhodamine 6G, having as scatterers butterfly-like TiO(2) nanomembranes (TiO(2)-NM) supported on a glass substrate. The feedback mechanism for laser action is due to the multiple scattering of light by TiO(2)-NM rather than provided by localized variations of the refractive index in the polymer film. The above-threshold multiple spikes signature indicative of random laser emission with coherent feedback is confirmed. As nanomembranes are foreseen as new MEMS/NEMS building blocks, a new generation of combined active/passive photonic devices can be envisaged.

Aggregation processes and formation of silico-calco-alkaline gels under high ionic strength.

This paper presents a systematic in situ study of the process of formation of silico-calco-alkaline gels starting from a liquid colloidal solution containing different alkaline ions and different calcium concentration until the final gel state. The combined use of X-ray and neutron small-angle scattering (SAS) and dynamical rheometry techniques lead to a consistent description of the structure of the aggregates and of the mechanisms of aggregation involved in gel formation. SAS results indicate that the aggregates are fractal objects, their structure strongly depending on calcium ion concentration. The differences in gelation kinetics for systems containing different alkaline ions were attributed to the effects of repulsive forces acting on the external surfaces of the fractal aggregates. The high ionic strength of the studied sols induces a non-classical dependence of these forces on the counter ion size.