An extensive experimental search for solid forms of the antipsychotic compound olanzapine identified 60 distinct solid forms including three nonsolvated polymorphs, 56 crystalline solvates, and an amorphous phase. XPac analysis of the 35 experimental crystal structures (30 from this work and 5 from the CSD) containing olanzapine show that they contain a specific, dispersion-bound, dimer structure which can adopt various arrangements and accommodate diverse solvents to produce structures with a similar moderate packing efficiency to form I. The crystal energy landscape confirms the inability of olanzapine to pack with an efficiency of more than 70%, explains the role of solvent in stabilizing the solvate structures, and identifies a hypothetical structural type that offers an explanation for the inability to obtain the metastable forms II and III separately. The calculations find that structures that do not contain the observed dimer are thermodynamically feasible, suggesting that kinetic effects are responsible for all the observed structures being based on the dimer. Thus, this extensive screen probably has not found all possible physical forms of olanzapine, and further form diversity could be targeted with a better understanding of the role of kinetics in its crystallization.

The authors identify some key definitions of 'information literacy' and initiatives concerned with imparting information literacy skills. They identify limitations in taking an approach to information literacy which assumes that it can be boiled down to a list of skills. Alternative conceptions of information literacy are described. Previous research has identified a lack of information on how students experience and define information literacy. The authors describe the student response to a one-semester credit-bearing class in information literacy, taken by business students at the University of Strathclyde, and relate it to two models of information literacy. They go on to discuss two issues in the light of previous developments and their own research: appropriate pedagogic methods for educating for information literacy and information literacy as a discipline in its own right. They conclude by identifying further areas for research and by recommending that information scientists should lead the way in defining this growing area. 50 1 2

The molecular structure of tetra-tert-butyldiphosphine has been determined in the gas phase by electron diffraction using the new DYNAMITE method and in the crystalline phase by X-ray diffraction. Ab initio methods were employed to gain a greater understanding of the structural preferences of this molecule in the gas phase, and to determine the intrinsic P-P bond energy, using recently described methods. Although the P-P bond is relatively long [GED 226.4(8) pm; X-ray 223.4(1) pm] and the dissociation energy is computed to be correspondingly small (150.6 kJ mol(-1)), the intrinsic energy of this bond (258.2 kJ mol(-1)) is normal for a diphosphine. The gaseous data were refined using the new Edinburgh structure refinement program ed@ed, which is described in detail. The molecular structure of gaseous P(2)Bu(t)(4) is compared to that of the isoelectronic 1,1,2,2-tetra-tert-butyldisilane. The molecules adopt a conformation with C(2) symmetry. The P-P-C angles returned from the gas electron diffraction refinement are 118.8(6) and 98.9(6) degrees, a difference of 20 degrees, whilst the C-P-C angle is 110.3(8) degrees. The corresponding parameters in the crystal are 120.9(1), 99.5(1) and 109.5(1) degrees. There are also large deformations within the tert-butyl groups, making the DYNAMITE analysis for this molecule extremely important.

Silk nanoparticles are viewed as promising vectors for intracellular drug delivery as they can be taken up into cells by endocytosis and trafficked to lysosomes, where lysosomal enzymes and the low pH trigger payload release. However, the subsequent degradation of the silk nanoparticles themselves still requires study. Here, we report the responsiveness of native and PEGylated silk nanoparticles to degradation following exposure to proteolytic enzymes (protease XIV and α-chymotrypsin) and papain, a cysteine protease. Both native and PEGylated silk nanoparticles showed similar degradation behavior over a 20 day exposure period (degradation rate: protease XIV > papain ≫ α-chymotrypsin). Within 1 day, the silk nanoparticles were rapidly degraded by protease XIV, resulting in a ∼50% mass loss, an increase in particle size, and a reduction in the amorphous content of the silk secondary structure. By contrast, 10 days of papain treatment was necessary to observe any significant change in nanoparticle properties, and α-chymotrypsin treatment had no effect on silk nanoparticle characteristics over the 20-day study period. Silk nanoparticles were also exposed ex vivo to mammalian lysosomal enzyme preparations to mimic the complex lysosomal microenvironment. Preliminary results indicated a 45% reduction in the silk nanoparticle size over a 5-day exposure. Overall, the results demonstrate that silk nanoparticles undergo enzymatic degradation, but the extent and kinetics are enzyme-specific.

Silk is a promising biopolymer for biomedical and pharmaceutical applications due to its outstanding mechanical properties, biocompatibility and biodegradability, as well its ability to protect and subsequently release its payload in response to a trigger. While silk can be formulated into various material formats, silk nanoparticles are emerging as promising drug delivery systems. Therefore, this article covers the procedures for reverse engineering silk cocoons to yield a regenerated silk solution that can be used to generate stable silk nanoparticles. These nanoparticles are subsequently characterized, drug loaded and explored as a potential anticancer drug delivery system. Briefly, silk cocoons are reverse engineered first by degumming the cocoons, followed by silk dissolution and clean up, to yield an aqueous silk solution. Next, the regenerated silk solution is subjected to nanoprecipitation to yield silk nanoparticles - a simple but powerful method that generates uniform nanoparticles. The silk nanoparticles are characterized according to their size, zeta potential, morphology and stability in aqueous media, as well as their ability to entrap a chemotherapeutic payload and kill human breast cancer cells. Overall, the described methodology yields uniform silk nanoparticles that can be readily explored for a myriad of applications, including their use as a potential nanomedicine.

Presentation and applied case study of a system-wide workflow which supports rapid, systematic and efficient continuous seeded cooling crystallisation process design, with the aim to deliver a robust, consistent process with tight control of particle attributes.

Silk is now making inroads into advanced pharmaceutical and biomedical applications. Both bottom-up and top-down approaches can be applied to silk and the resulting aqueous silk solution can be processed into a range of material formats, including nanoparticles. Here, we demonstrate the potential of microfluidics for the continuous production of silk nanoparticles with tuned particle characteristics. Our microfluidic-based design ensured efficient mixing of different solvent phases at the nanoliter scale, in addition to controlling the solvent ratio and flow rates. The total flow rate and aqueous : solvent ratios were important parameters affecting yield (1 mL min À1 > 12 mL min À1 ). The ratios also affected size and stability; a solvent : aqueous total flow ratio of 5 : 1 efficiently generated spherical nanoparticles 110 and 215 nm in size that were stable in water and had a high beta-sheet content. These 110 and 215 nm silk nanoparticles were not cytotoxic (IC50 > 100 mg mL À1 ) but showed size-dependent cellular trafficking. Overall, microfluidicassisted silk nanoparticle manufacture is a promising platform that allows control of the silk nanoparticle properties by manipulation of the processing variables.

Drug discovery would be enriched if fuller use was made of the chemistry of natural products.