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A non-destructive neutron analysis technique performed at the IMAT beamline of the STFC (Science and Technology Facility Council), UK, is presented. In this experiment, neutrons of different energy have been exploited to obtain a tomographic reconstruction of a biomineralic sample, more specifically a cultured pearl, by using a time-resolving pixel camera, the MicroChannel Plate (MCP) detector, utilizing an array of 2 × 2 Timepix readout chips. The MCP camera is capable of energy-resolved two-dimensional mapping of neutron transmission with a spatial resolution of ~ 55 μm. By using a Simultaneous Iterative Reconstruction Technique (SIRT), virtual sections of the internal part of the sample have been created, thus revealing several features inside its bulk. The crystallographic phase map via Bragg edge analysis, showing a phase fraction distribution on the entire specimen, has been generated as well. Finally, 3D volume rendering of the pearl is presented.

Neutron Tomography (NT) is an established technique to non-destructively investigate the inner structure of a wide range of objects. The major drawback of NT is the long acquisition time required to perform a tomographic scan compared to an X-ray Computed Tomography (CT) scan, due to the limited particle flux of the existing neutron sources. Therefore, in the NT field there is great interest in the reduction of scan time, dictated by the high neutrons production cost, aimed at optimizing the beamtime use at neutron imaging beamlines. A way for decreasing the total scan time is to reduce the number of projections. Generally, iterative reconstruction methods have advantages over analytical algorithms, such as the widely used Filtered Back-Projection (FBP), when data are noisy and limited. This research is focused on the comparative analysis of different reconstruction techniques, aimed at finding the data processing procedure suitable for NT, that reduces the scan time without reduction of the reconstructed image quality. For this purpose, a phantom sample was analysed by means of a white beam NT performed at the IMAT beamline, ISIS Neutron Source, U.K . Experimental data were used to test the performances of the FBP algorithm and different iterative reconstruction methods as a function of the number of projections and for different setups of the imaging system. The reconstructed images were quantitatively compared in terms of image quality indexes and the benefits of iterative methods for the limited data problem are discussed.

Nanoparticles (NPs) formed from polymers conjugated with bisphosphonates (BPs) allow the bone targeting of loaded drugs, such as doxorubicin, for the treatment of skeletal tumours. The additional antiosteoclastic effect of the conjugated BP could contribute to the inhibition of tumour-associated bone degradation. With this aim, we have produced NPs made of poly(d,l-lactide-co-glycolide) (PLGA) conjugated with alendronate (ALE). To show if ALE retained the antiosteoclastic properties after the conjugation with PLGA and the production of NPs, we treated human osteoclasts, derived from circulating precursors, with PLGA-ALE NPs and compared the effects on actin ring generation, apoptosis and type-I collagen degradation with those of free ALE and with NPs made of pure PLGA. PLGA-ALE NPs disrupted actin ring, induced apoptosis and inhibited collagen degradation. Unexpectedly, also NPs made of pure PLGA showed similar effects. Therefore, we cannot exclude that in addition to the observed antiosteoclastic activity dependent on ALE in PLGA-ALE NPs, there was also an effect due to pure PLGA. Still, as PLGA-ALE NPs are intended for the loading with drugs for the treatment of osteolytic bone metastases, the additional antiosteoclastic effect of PLGA-ALE NPs, and even of PLGA, may contribute to the inhibition of the disease-associated bone degradation.

Background & aims: Osteotropic drug-delivery systems have been proposed as a means to provide drugs with affinity to bone tissues. Drugs or proteins have been linked chemically to bone-seeking agents, such as bisphosphonates (BPs); alternatively, drug-loaded nanoparticles have been used to target specific tissues, such as tumor areas. In our current research, these approaches were merged by synthesizing a novel bone-seeking polymer conjugate, from which targetable nanoparticles can be produced. Materials & methods: An amino-BP, alendronate (ALE) was bound covalently to a biodegradable polymer, poly(lactic-co-glycolide) (PLGA), containing a free end carboxylic group. Blood compatibility and cytotoxicity were assessed in vitro. Results & discussion: By a classical solvent-evaporation method, nanoparticles with a mean size of 200–300 nm were prepared from the conjugate; sterilization was achieved by γ-irradiation, confirming their potential as injectable drug nanocarriers. Owing to the presence of the BP residue, PLGA–ALE nanoparticles were adsorbed onto hydroxyapatite to a higher extent than pure PLGA nanoparticles. The PLGA–ALE conjugate did not induce either hemolysis or alterations of the plasmatic phase of coagulation, or cytotoxic effects on endothelial cells and trabecular osteoblasts. Conclusion: The prepared conjugate represents a novel biomaterial that is able to provide nanoparticles, which can be further loaded with drugs, such as anticancer agents, and addressed to osteolytic or other bone diseases.

Nanoparticles made of a conjugate of poly(D,L-lactide-co-glycolide) with alendronate (PLGA-ALE NPs), were prepared by emulsion/solvent evaporation technique. The conjugation yield, determined by MALDI TOF analysis, was 30-35%. PLGA-ALE NPs size, evaluated by photon correlation spectroscopy, was 198.7+/-0.2 nm. Haemocompatibility studies using different concentrations of PLGA-ALE NPs did not show any significant effect on haemolysis, leukocyte number, platelet activation, APTT and complement consumption, in comparison with blood incubated with phosphate buffered saline (PBS). A significant reduction of the prothrombin activity was demonstrated after incubation with 560 microg/ml of PLGA-ALE NPs; a significant increase was observed at the highest dilutions. The viability of human umbilical vein endothelial cells and bone marrow stromal cells (BMSC), evaluated through the neutral red test, was not affected by PLGA-ALE NPs. There were no significant differences in cell-associated alkaline phosphatase between BMSC incubated with PLGA-ALE NP- and PBS-added media. These results demonstrated that PLGA-ALE NPs had an acceptable degree of blood compatibility and were not cytotoxic; therefore, they may be considered suitable for intravenous administration.