Aerosol delivery of antibiotics via nanoparticles may provide a means to improve
drug delivery and increase patient compliance, thus reducing the severity of
individual illnesses, the spread of epidemics, and possibly even retarding antibiotic
resistance.
Delivery of antibiotics via nanoparticles has shown promise as a drug delivery
mechanism, particularly for controlled release or depot delivery of drugs to
decrease the number of doses required to achieve a clinical effect. The effectiveness
of this delivery mechanism has not been confirmed directly either in infection
models or in patients, but according to new data to be presented on Tuesday,
May 19, at the American Thoracic
Society's 105th International Conference in San Diego, this delivery technique
appears indeed promising.
Carolyn L. Cannon, M.D., Ph.D. from Washington University School of Medicine,
and colleagues from the Center for Silver Therapeutics Research at the University
of Akron in OH investigated the efficacy of nanoparticle-encapsulated silver-based
antibiotics for treating pulmonary infections in a mouse model of pneumonia.
Treatment with antibiotic-laden nanoparticles effectively eliminated respiratory
infections in mice that had been inoculated with Pseudomona aeroginosa, a common
bacterial species that often infects the respiratory tract in humans, particularly
immunocompromised patients, ventilated patients or those with cystic fibrosis.
Infected mice that inhaled aerosolized nanoparticles encapsulating silver carbene
complexes (SCCs), a novel class of silver-based antimicrobials with broad-spectrum
activity, showed a significant survival advantage over the control mice that
received nanoparticles without the SCCs. Treated mice also had decreased lung
bacterial burden and spread, compared to the control mice. Moreover, the treatment
with nanoparticles occurred once every 24 hours, a regimen that is known to
increase compliance in human patients, versus the usual dosing interval of inhaled
antibiotics for P. aeruginosa, which is twice daily.
"We were surprised and thrilled to see a 100 percent survival advantage
in mice treated daily with SCC22-loaded nanoparticles at doses significantly
lower than those used to achieve a similar survival advantage in twice-daily
dosing of unencapsulated SCC22. During a 72 hour period, all of the infected
control mice died, whereas all of the mice that received just two doses of SCC22-loaded
nanoparticles spaced 24 hours apart survived."
"My collaborators, Wiley Youngs, Ph.D., and Yang Yun, Ph.D., and I are
eager to complete toxicity studies that would enable us to start clinical trials,"
said Dr. Cannon. "While the mouse studies are tantalizing, the goal that
propels our research is realizing the promise of these novel antibiotics and
delivery mechanisms through an analogous survival advantage in patients."
Posted May 19th, 2009
