Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis

Effect of instillation volume and form of anesthesia

Mark Miller, Jennifer M. Stabenow, Jyothi Parvathareddy, Andrew J. Wodowski, Thomas P. Fabrizio, Xiaowen R. Bina, Lillian Zalduondo, James E. Bina

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 μl 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 a dose volume of 50 μl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane) vs. parenteral (ketamine/xylazine) anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique.

Original languageEnglish (US)
Article numbere31359
JournalPloS one
Volume7
Issue number2
DOIs
StatePublished - Feb 24 2012

Fingerprint

Francisella tularensis
anesthesia
Vaccines
Visualization
Anesthesia
lungs
Lung
mice
live vaccines
Xylazine
Isoflurane
Ketamine
Photorhabdus
Francisella
dosage
Infection
Photorhabdus luminescens
infection
Imaging systems
tularemia

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis : Effect of instillation volume and form of anesthesia. / Miller, Mark; Stabenow, Jennifer M.; Parvathareddy, Jyothi; Wodowski, Andrew J.; Fabrizio, Thomas P.; Bina, Xiaowen R.; Zalduondo, Lillian; Bina, James E.

In: PloS one, Vol. 7, No. 2, e31359, 24.02.2012.

Research output: Contribution to journalArticle

Miller, Mark ; Stabenow, Jennifer M. ; Parvathareddy, Jyothi ; Wodowski, Andrew J. ; Fabrizio, Thomas P. ; Bina, Xiaowen R. ; Zalduondo, Lillian ; Bina, James E. / Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis : Effect of instillation volume and form of anesthesia. In: PloS one. 2012 ; Vol. 7, No. 2.
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