US Funds Development of an Inhaled Form of Gentamicin
In the event of a bioterrorist attack, the Centers for Disease Control and Prevention considers six Category A biological agents as the most likely culprits. These agents include botulinum toxin, anthrax, viral hemorrhagic fevers, plague, smallpox, and tularemia. The high morbidity and mortality give these biohazardous threat agents a particular potential for public health impact.
NanoGENTTM, an inhaled formulation of the broad-spectrum antibiotic, gentamicin, provides a potential treatment for bioterrorist threat agents, such as those that cause tularemia and plague. Gentamicin is a bactericidal aminoglycoside antibiotic that binds to the 30S ribosome of gram-negative bacteria and thereby inhibits protein synthesis.
According to the manufacturer, NanoGENTTM provides several potential advantages over traditional delivery mechanisms such as intravenous administration. These include: 1) higher shelf-life stability, 2) better control of particle size and deposition efficiency, 3) control of cell uptake and targeting, 4) controlled release-rates, and 5) increased systemic bioavailability. Descriptions of these advantages may be found on the Nanotherapeutics, Inc. website at: http://www.nanotherapeutics.com/ nanotechnology.php.
Perhaps the most beneficial advantage of inhalational gentamicin might occur during situations requiring mass post-exposure prophylaxis, such as large-scale biological agent release. This advantage is in the relative ease of administration and non-invasive nature of the drug delivery system. Further “advantages of inhaled therapy include direct drug delivery to the diseased organ, targeting to alveolar macrophages harboring the bacteria, reduced risk of systemic toxicity, and improved patient compliance.” More detailed information regarding these advantages may be found in the following publication: Pandey, R., and Khuller, G.K. “Antitubercular inhaled therapy: opportunities, progress, and challenges.” J Antimicrob Chemo. (2005) 55: 430-435. Potential disadvantages that occurred with older versions of inhaled antibiotics several decades ago, including aminoglycosides, must be anticipated and monitored for closely.
The lack of FDA-licensed vaccines or immunoglobulin for either tularemia or plague, as well as the potential for person-to-person transmission of plague pneumonia, leave antibiotics as the only presently available therapeutic countermeasure. Therefore, novel forms of antibiotics, such as NanoGENTTM, may contribute to the advancement of our current biodefense countermeasures.
Megan Hofmeister, Christine SooHoo, Courtney Tauscher, Ray Webber, and Wade Greening
Graduate Students in the Master of Science (M.S.) Program in
Biohazardous Threat Agents and Emerging Infectious Diseases, Department of Microbiology
and Immunology, Georgetown University Medical Center. MICB-523 Course: “
Biodefense Public Health Countermeasures” taught by Daniel R. Lucey, MD, MPH,
Director of the Center Biological Counterterrorism and Emerging Diseases, EROne
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