Purdue University researchers have invented a new way of delivering two antibiotics (colistin and ciprofloxacin) deep into the lungs of cystic fibrosis (CF) patients, enabling much more effective killing of antibiotic-resistant bacteria without exposing patients to high systemic doses of these therapies.
“We are providing a promising option to fight the global crisis of antimicrobial resistance,” Qi (Tony) Zhou, PhD, assistant professor at Purdue’s College of Pharmacy, who led the research team, said in a press release.
Respiratory infections caused by multidrug-resistant bacteria in CF patients can be deadly because they are resistant to most available antibiotics. In addition, therapies given intravenously (by injection into the vein) or orally have a hard time reaching the lungs, potentially requiring high doses for the therapy to be effective.
Last-resort antibiotics can still be effective, but these can be very toxic if they are given systemically. Colistin, for example, can damage the kidneys.
The existing alternative is to nebulize the antibiotics and deliver them directly into the lungs, which increases their local concentrations while reducing the risk of systemic toxicity. However, this requires expensive and complicated delivery devices, and prolonged administration times.
Now, Zhou’s team has succeeded in combining two antibiotics — colistin and ciprofloxacin — into a single particle that can be delivered as a dry powder.
According to the team, with this new formulation, more than 60 percent of the antibiotics reach the lungs, as opposed to only 10 percent with a jet nebulizer. In addition, the dry formulation offers improved chemical stability, and it is easier to use than conventional inhalation products.
“It has been a worldwide challenge to incorporate two antibiotics with different chemical properties into a single particle. Our novel formulation allows for a much more effective killing of drug-resistant bacteria in the deep lungs as two synergistic antibiotics can be simultaneously delivered to the same infection site,” Zhou said.
The team believes this technology can be applied to several antibiotic and compound combinations, potentially saving tens of thousands of lives from several deadly lung infections, including those affecting CF patients and people with ventilator-assisted pneumonia.
The Purdue Office of Technology Commercialization has filed a patent for the new technology, and researchers are looking for partners to continue its development.
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