Drug-excipient behavior in polymeric amorphous solid dispersions

Amorphous drug delivery systems are increasingly utilized to enhance aqueous solubility and oral bioavailability. However, they lack physical and/or chemical stability. One of the most common ways of stabilizing an amorphous form is by formulating it as an amorphous solid dispersion. This review focuses on polymeric amorphous solid dispersions wherein polymers are used as excipients to stabilize the amorphous form. A brief introduction to the basic concepts of amorphous systems such as glass transition temperature and the solubility advantage of amorphous systems is provided. Additionally, information on types of polymers used for the development of amorphous solid dispersions, their structural attributes and mechanisms of stabilization are presented here. Molecular aspects of drug-polymer miscibility and drugpolymer interactions are also discussed

Central nervous system immune interactome is a function of cancer lineage, tumor microenvironment, and STAT3 expression.

BACKGROUNDImmune cell profiling of primary and metastatic CNS tumors has been focused on the tumor, not the tumor microenvironment (TME), or has been analyzed via biopsies.METHODSEn bloc resections of gliomas (n = 10) and lung metastases (n = 10) were analyzed via tissue segmentation and high-dimension Opal 7-color multiplex imaging. Single-cell RNA analyses were used to infer immune cell functionality.RESULTSWithin gliomas, T cells were localized in the infiltrating edge and perivascular space of tumors, while residing mostly in the stroma of metastatic tumors. CD163+ macrophages were evident throughout the TME of metastatic tumors, whereas in gliomas, CD68+, CD11c+CD68+, and CD11c+CD68+CD163+ cell subtypes were commonly observed. In lung metastases, T cells interacted with CD163+ macrophages as dyads and clusters at the brain-tumor interface and within the tumor itself and as clusters within the necrotic core. In contrast, gliomas typically lacked dyad and cluster interactions, except for T cell CD68+ cell dyads within the tumor. Analysis of transcriptomic data in glioblastomas revealed that innate immune cells expressed both proinflammatory and immunosuppressive gene signatures.CONCLUSIONOur results show that immunosuppressive macrophages are abundant within the TME and that the immune cell interactome between cancer lineages is distinct. Further, these data provide information for evaluating the role of different immune cell populations in brain tumor growth and therapeutic responses.FUNDINGThis study was supported by the NIH (NS120547), a Developmental research project award (P50CA221747), ReMission Alliance, institutional funding from Northwestern University and the Lurie Comprehensive Cancer Center, and gifts from the Mosky family and Perry McKay. Performed in the Flow Cytometry & Cellular Imaging Core Facility at MD Anderson Cancer Center, this study received support in part from the NIH (CA016672) and the National Cancer Institute (NCI) Research Specialist award 1 (R50 CA243707). Additional support was provided by CCSG Bioinformatics Shared Resource 5 (P30 CA046592), a gift from Agilent Technologies, a Research Scholar Grant from the American Cancer Society (RSG-16-005-01), a Precision Health Investigator Award from University of Michigan (U-M) Precision Health, the NCI (R37-CA214955), startup institutional research funds from U-M, and a Biomedical Informatics & Data Science Training Grant (T32GM141746)

Latest results on the production of hadronic resonances in ALICE at the LHC

Measurement of short-lived hadronic resonances are used to study different aspects of particle production and collision dynamics in pp, p–A and relativistic heavy-ion collisions. The yields of resonances are sensitive to the competing processes of hadron rescattering and regeneration, thus making these particles unique probes of the properties of the late hadronic phase. Measurements of resonances with different masses and quantum numbers also provide insight into strangeness production and processes that determine the shapes of particle momentum spectra at intermediate transverse momenta, as well as the species dependence of hadron suppression at high momentum. We present the comprehensive set of results in the ALICE experiment with unprecedented precision for ρ(770)0, K∗(892), φ(1020), Σ(1385)±, Λ(1520), and Ξ(1530)0 production in pp, p–Pb, Xe–Xe and Pb–Pb collisions in the energy range √sNN = 2.76-13 TeV, including the latest measurements from LHC Run 2. The obtained results are used to study the system-size and collision-energy evolution of transverse momentum spectra, particle ratios and nuclear modification factors and to search for the onset of collectivity in small collision systems. We compare these results to lower energy measurements and model calculations where available.publishedVersio