Cholesterol levels affect the performance of aunps-decorated thermo-sensitive liposomes as nanocarriers for controlled doxorubicin delivery

Stimulus-responsive liposomes (L) for triggering drug release to the target site are particularly useful in cancer therapy. This research was focused on the evaluation of the effects of cholesterol levels in the performance of gold nanoparticles (AuNPs)-functionalized L for controlled doxorubicin (D) delivery. Their interfacial and morphological properties, drug release behavior against temperature changes and cytotoxic activity against breast and ovarian cancer cells were studied. Langmuir isotherms were performed to identify the most stable combination of lipid components. Two mole fractions of cholesterol (3.35 mol% and 40 mol%, L1 and L2 series, respectively) were evaluated. Thin-film hydration and transmembrane pH-gradient methods were used for preparing the L and for D loading, respectively. The cationic surface of L allowed the anchoring of negatively charged AuNPs by electrostatic interactions, even inducing a shift in the zeta potential of the L2 series. L exhibited nanometric sizes and spherical shape. The higher the proportion of cholesterol, the higher the drug loading. D was released in a controlled manner by diffusion-controlled mechanisms, and the proportions of cholesterol and temperature of release media influenced its release profiles. D-encapsulated L preserved its antiproliferative activity against cancer cells. The developed liposomal formulations exhibit promising properties for cancer treatment and potential for hyperthermia therapy.Ministerio de Ciencia e Innovación CTQ2014- 57515-C2-

Definition and validation of a radiomics signature for loco-regional tumour control in patients with locally advanced head and neck squamous cell carcinoma

Purpose: To develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Material and methods: Pre-treatment CT images of 318 patients with locally advanced HNSCC were col-lected. Four-hundred forty-six features were extracted from each primary tumour volume and then fil-tered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed. Results: For the clinical baseline signature, only the primary tumour volume was selected. The final sig-nature combined the tumour volume with two independent radiomics features. It achieved moderatel

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

L

Bimodal release of olanzapine from lipid microspheres

Olanzapine was formulated as 10% (w/w) mixture with cutina to which stearic acid was added, ranging from 10% to 90% (w/w) of the total mass to control the drug release. The molten mixtures were processed by ultrasound-assisted spray-congealing technique, obtaining solid microspheres. The drug is stable under these conditions and only a partial miscibility in the solid state was observed by DSC between the two fatty materials with two separated melting endotherms in the thermograms: this can be due to the presence of two phases inside the solid dispersion. Olanzapine is distributed into the two phases according to its partition coefficient: two phases make the system less suitable to crystallization of the drug; the loading of the drug could reach saturation with difficulty and the rate of the olanzapine release is differentiated, since the drug is released from two different carriers. Dissolution profiles suggest occurrence of a bimodal release, where each portion of the release profile is linear and the slope increases with a higher content of stearic acid in the carrier mixture, that behaves as a release promoter. Tests were also carried out with palmitic and lauric acids for comparison and also for systems in the absence of ultrasound

Deliverable D5.4 - Resilience and Vulnerability Assessment

This document describes the SmartHubs Resilience Tool, developed within the SmartHubs project. The tool analyses the accessibility and network connectivity impacts of mobility hubs on the resilience of urban public transportation networks. The development of the task described in this deliverable comprises three phases: (1) the methodological development of a study combining spatial interaction, accessibility and network analysis; (2) the development of the SmartHubs Resilience Tool, by integrating the three approaches, and (3) the application of the tool to the urban areas where SmartHubs Living Labs are located, including scenario analyses based on potential changes in the wider transport network. The tool, which relies on public transport and bike sharing data, is made up of two components: a first one providing network analysis-based indicators, such as efficiency and betweenness; a second one allowing to compute accessibility indicators – emerging from conventional spatial interaction/transport models – for the geographical area under analysis. Transport connectivity and area accessibility are two concepts that are closely intertwined, as both influence the ease with which individuals can reach specific locations. A well-connected transport network can facilitate the movement of people (or goods), thereby reducing travel times and increasing efficiency, and in turn, improving area accessibility. In this report, an evaluation of the cities associated to each of the SmartHubs Living Labs is provided, using the above-mentioned indicators. A network representation of the local urban public transport supply is developed, to which origin-destination (OD) matrices (when available) containing flows of mobility throughout each city is coupled. Flows are distributed over the public transport network, allowing us to observe more in detail potential critical aspects of the network. Moreover, station-based sharing services (shared bikes) are added to this network, further enriching the representation of mobility options through the cities. Finally, scenarios are developed where, for each city, different types of disruptions or more generally changes to service (e.g. the introduction of further bike stations) are simulated. For each scenario, network and accessibility metrics are re-computed, therefore allowing to measure the effect of such disruptions on the network, with or without the presence of bike sharing services. The general finding of the simulations carried out is that bike-sharing stations located in correspondence of public transport stops can be of great help in improving the general resilience of urban mobility to disruptions (i.e. they increase the global efficiency of the network). Furthermore, we show that the effect of disruptions – in terms of the induced reduction in the efficiency of the network – is significantly reduced when bike-sharing services are available, compared to when they are not. The research reported in this report lays the foundation for more work in urban mobility taking into account the importance of network resilience and accessibility, in particular towards guiding local policymakers and urban/transport planners in critical decisions regarding the integration of public transport and micromobility (e.g., mobility as a service) and the authorization of alternative (and sustainable) transport modes

Release of indomethacin from ultrasound dry granules containing lactose-based excipients

Physical mixtures were prepared containing indomethacin and beta-lactose and alpha-lactose-based excipients (Ludipress and Cellactose). The mixtures were compacted with the aid of ultrasound, obtaining tablets, which were milled and sieved. Granules thus obtained were examined by optical microscopy and differential scanning calorimetry. The intense yellow color of the granules and the absence of indomethacin peak in thermograms suggest important modifications of indomethacin physical state; the drug thus modified appears to be spread on the excipient particle surface as a thin film, giving a lustrous appearance. No influence of ultrasound was observed on phase transition concerning lactose; only loss of water was important under high energy ultrasound. Dissolution profiles suggest an increased release of the drug from the systems treated with ultrasound at high energy, with respect to a traditional compaction; while no difference could be evidenced among the three excipients that, however, appear all suitable for this ultrasound-aided direct compression process