visualization of murine intranasal dosing efficiency using luminescent francisella tularensis effect of instillation volume and form of anesthesia可视化的小鼠鼻内给药效率使用发光土拉杆菌内滴注法体积和形式的麻醉效果.pdfVIP

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia 1 1 1 1 Mark A. Miller *, Jennifer M. Stabenow , Jyothi Parvathareddy , Andrew J. Wodowski , 1,2 1 1 1 Thomas P. Fabrizio , Xiaowen R. Bina , Lillian Zalduondo , James E. Bina 1The University of Tennessee Health Science Center, Memphis, Tennessee, United States of America, 2 St Jude Children’s Research Hospital, Memphis, Tennessee, United States of America Abstract Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS) infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 ml routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required