Article thumbnail

Visualization of Murine Intranasal Dosing Efficiency Using Luminescent Francisella tularensis: Effect of Instillation Volume and Form of Anesthesia

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

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

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3286442
Provided by: PubMed Central

Suggested articles

Citations

  1. (2010). A mouse model of lethal infection for evaluating prophylactics and therapeutics against Monkeypox virus.
  2. (2005). A mutant of Francisella tularensis strain SCHU S4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine. Infection and immunity 73:
  3. (2007). A novel and simple method for endotracheal intubation of mice.
  4. (2005). A novel method for endotracheal intubation of mice and rats used in imaging studies.
  5. (2011). Airway epithelial MyD88 restores control of Pseudomonas aeruginosa murine infection via an IL-1-dependent pathway.
  6. (2009). An improved simple method of mouse lung intubation.
  7. (2009). Analgesic effect from Ibuprofen nanoparticles inhaled by male mice.
  8. (2006). Applicability of an ultrasonic nebulization system for the airways delivery of beclomethasone dipropionate in a murine model of asthma.
  9. (2010). Attenuated response of aged mice to respiratory Francisella novicida is characterized by reduced cell death and absence of subsequent hypercytokinemia.
  10. (2011). Bordetella pertussis infection exacerbates influenza virus infection through pertussis toxinmediated suppression of innate immunity.
  11. (2011). c-di-GMP protects against intranasal Acinetobacter baumannii infection in mice by chemokine induction and enhanced neutrophil recruitment.
  12. (2011). CD8+ cells enhance resistance to pulmonary serotype 3 Streptococcus pneumoniae infection in mice.
  13. (2008). Characterization and deposition of respirable large- and small-particle bioaerosols.
  14. (2011). Chlamydophila pneumoniae induces production of the defensin-like MIG/CXCL9, which has in vitro antichlamydial activity.
  15. (2011). Combining vaccination and postexposure CpG therapy provides optimal protection against lethal sepsis in a biodefense model of human melioidosis.
  16. (2011). Comparative effects of carbapenems on bacterial load and host immune response in a Klebsiella pneumoniae murine pneumonia model. Antimicrobial agents and chemotherapy 55:
  17. (2010). Construction of a bioluminescence reporter plasmid for Francisella tularensis.
  18. (2000). Cytokine mRNAs in the nasal-associated lymphoid tissue during influenza virus infection and nasal vaccination.
  19. (2008). Differential pathogenesis of cowpox virus intranasal infections in mice induced by low and high inoculum volumes and effects of cidofovir treatment.
  20. (2004). Direct visual instillation as a method for efficient delivery of fluid into the distal airspaces of anesthetized mice.
  21. (2002). Distribution of intranasal instillations in mice: effects of volume, time, body position, and anesthesia.
  22. (2011). Efficacy of vaccination strategies against intranasal challenge with Brucella abortus in BALB/c mice.
  23. (2011). Enhanced virulence of Chlamydia muridarum respiratory infections in the absence of TLR2 activation.
  24. (1977). Experimental pulmonary infection of mice by tracheal intubation of Pseudomonas aeruginosa: the use of antineoplastic agents to overcome natural resistance.
  25. (2011). Induction of protection in mice against a respiratory challenge by a vaccine formulated with the Chlamydia major outer membrane protein adjuvanted with IC31(R).
  26. (2003). Innate and adaptive immune responses to an intracellular bacterium, Francisella tularensis live vaccine strain. Microbes and infection/Institut
  27. (2011). Intranasal vaccination with pneumococcal surface protein A plus poly(I:C) protects against secondary pneumococcal pneumonia in mice.
  28. (2011). Kinase activity profiling of pneumococcal pneumonia.
  29. (2009). Laboratory Animal Anesthesia.
  30. (2011). Lactobacillus-mediated priming of the respiratory mucosa protects against lethal pneumovirus infection.
  31. (2008). Microscopic wire guide-based orotracheal mouse intubation: description, evaluation and comparison with transillumination.
  32. (2011). Mucosal vaccination with a multivalent, live-attenuated vaccine induces multifactorial immunity against Pseudomonas aeruginosa acute lung infection. Infection and immunity 79:
  33. (2011). Nitric oxide synthase activity has limited influence on the control of Coccidioides infection in mice.
  34. (2011). Outer Membrane Protein A (OmpA) of Shigella flexneri 2a, Induces Protective Immune Response in a Mouse Model.
  35. (2011). Outer membrane vesicles obtained from Bordetella pertussis Tohama expressing the lipid A deacylase PagL as a novel acellular vaccine candidate.
  36. (2011). Overexpression of sICAM-1 in the alveolar epithelial space results in an exaggerated inflammatory response and early death in Gram negative pneumonia.
  37. (1961). Prophylactic effectiveness of live and killed tularemia vaccines. I. Production of vaccine and evaluation in the white mouse and guinea pig.
  38. (1994). Prophylactic efficacy of aerosolized liposomal (AmBisome) and non-liposomal (Fungizone) amphotericin B in murine pulmonary aspergillosis.
  39. (2011). Recombinant human tissue factor pathway inhibitor exerts anticoagulant, antiinflammatory and antimicrobial effects in murine pneumococcal pneumonia. Journal of thrombosis and haemostasis : JTH 9: 122–132. Pneumonic Delivery via Intranasal Instillation
  40. (2011). Role of neutrophils and NADPH phagocyte oxidase in host defense against respiratory infection with virulent Francisella tularensis in mice.
  41. (1999). Short ragweed allergen induces eosinophilic lung disease in HLA-DQ transgenic mice.
  42. (2011). Specific inhibition of nitric oxide synthases at different time points in a murine model of pulmonary sepsis. Biochemical and biophysical research communications 404:
  43. (2011). Stenotrophomonas maltophilia strains replicate and persist in the murine lung, but to significantly different degrees.
  44. (1999). The importance of the diluent for airway transport of toluene diisocyanate following intranasal dosing of mice.
  45. (2011). The integrins Mac-1 and alpha4beta1 perform crucial roles in neutrophil and T cell recruitment to lungs during Streptococcus pneumoniae infection.
  46. (2011). The role of reactive oxygen intermediates in experimental coccidioidomycois in mice.
  47. (2001). Tissue distribution of radioactivity following intranasal administration of radioactive microspheres.
  48. (2002). Tracking the tissue distribution of marker dye following intranasal delivery in mice and chinchillas: a multifactorial analysis of parameters affecting nasal retention.
  49. (2001). Tularemia as a biological weapon: medical and public health management.
  50. (1961). Tularemia vaccine study. I. Intracutaneous challenge.
  51. (1961). Tularemia vaccine study. II. Respiratory challenge.
  52. (2003). Video-assisted orotracheal intubation in mice.

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.