Pharmacokinetics, Metabolism, and Partial Biodistribution of “Pincer Therapeutic” Nitazoxanide in Mice following Pulmonary Delivery of Inhalable Particles

Nitazoxanide (NTZ) induces autophagy in mammalian cells and also has mycobactericidal activity, displaying a two-pronged therapeutic effect, on the host as well as the pathogen. The pharmacokinetics and biodistribution of inhaled NTZ were investigated. Particles containing NTZ in a matrix of PLGA were prepared by spray drying. HPLC and LC–MS/MS methods were developed and validated. Particles were administered as inhalations to mice. Drug concentrations in plasma and tissues were estimated at different time points. Drug loading (∼36%), entrapment efficiency (>90%), and the conversion of NTZ into metabolites in plasma and lung homogenates were assessed satisfactorily by HPLC. NTZ pharmacokinetics and biodistribution following intravenous administration or inhalation were established by LC–MS. NTZ converted into tizoxanide (99% in 30 min) and other metabolites. Pulmonary delivery of NTZ entrapped in particles increased the half-life of the drug by factors of 3, 12, and 200 in the plasma, lung tissue, and alveolar macrophages, respectively. Targeted delivery and prolonged lung retention along with dose sparing of the kidneys was observed upon pulmonary delivery as compared to intravenous administration

Mechanically controlling the reversible phase transformation from zinc blende to wurtzite in AlN

<p>III–V and other binary octet semiconductors often take two phase forms—wurtzite (wz) and zinc blende (zb) crystal structures—with distinct functional performance at room temperature. Here, taking AlN as a representative III–V compound, we investigate how to control the synthesized phase structure to either wz or zb phase by tuning the interfacial strain. By applying <i>in situ</i> mechanical tests at atomic scale in a transmission electron microscope, we observed the reversible phase transformation from zb to wz, and characterized the transition path—the collective glide of Shockley partials on every two {111} planes of the zb AlN.</p> <p><b>IMPACT STATEMENT</b></p> <p>The <i>innovation</i> of this paper is that a new type of plastic-deformation-driven reversible phase transition in AlN has been captured at atomic scale.</p

Fluid and Resistive Tethered Lipid Membranes on Nanoporous Substrates

Cell membranes perform important biological roles including compartmentalization, signaling, and transport of nutrients. Supported lipid membranes mimic the behavior of cell membranes and are an important model tool for studying membrane properties in a controlled laboratory environment. Lipid membranes may be supported on solid substrates; however, protein and lipid interactions with the substrate typically result in their denaturation. In this report, we demonstrate the formation of intact lipid membranes tethered on nanoporous metal thin films obtained via a dealloying process. Uniform lipid membranes were formed when the surface defect density of the nanoporous metal film was significantly reduced through a two-step dealloying process reported here. We show that the tethered lipid membranes on nanoporous metal substrates maintain both fluidity and electrical resistivity, which are key attributes to naturally occurring lipid membranes. The lipid assemblies supported on nanoporous metals provide a new platform for investigating lipid membrane properties, and potentially membrane proteins, for numerous applications including next generation biosensor platforms, targeted drug-delivery, and energy harvesting devices

Discovery-Based Science Education: Functional Genomic Dissection in Drosophila by Undergraduate Researchers

Discovery-Based Science Education: Functional Genomic Dissection in Drosophila by Undergraduate Researcher

Example of the Type of Data Available from the Online Database (http://www.bruinfly.ucla.edu)

<p>Example of the Type of Data Available from the Online Database (<a href="http://www.bruinfly.ucla.edu" target="_blank">http://www.bruinfly.ucla.edu</a>)</p

Representative Pictures from the Laboratory Section of the Course

<p>Representative Pictures from the Laboratory Section of the Course</p