New Treatment for Lung Infections in Cystic Fibrosis Up to 100,000-Fold More Effective

A novel biometric nanostructured material used to treat lung infections in cases of severe cystic fibrosis increased its efficacy by up to 100,000-fold over the current treatment, according to papers published in both Small and ACS Infectious Diseases.

In the Small paper, investigators from the University of South Australia described how they used an advanced, biologically-relevant co-culture model of human cystic fibrosis bronchial epithelial cells that were infected with Pseudomonas aeruginosa (P. aeruginosa), which is a cause of persistent and chronic lung infections in patients with cystic fibrosis. The treatment used to treat P. aeruginosa is the antibiotic Tobramycin, however its efficacy is severely limited due to permeability problems. The novel nanotech approach was designed to enhance efficacy in treatment for P. aeruginosa due to increased permeability.

In testing with the bronchial epithelial cells, the nanotech eradicated P. aeruginosa after 2 doses, the investigators reported, which was a 100-fold improvement over the Tobramycin. When Tobramycin is paired with an antibiotic that permeates biofilms such as ciprofloxacin, the nanotech still performed.

The study authors indicated that the nanotech had enhanced penetration of Tobramycin across the biofilm barrier, but not through healthy lung cells, which allows for increased concentration of the antibiotic at the site of infection. Therefore, this strategy would enable the administration of lower doses and a reduced toxicity, they wrote.

“Tobramycin is commonly used to treat these infections but increasingly antibiotics are failing to make any significant difference to lung infections, leaving sufferers requiring life-long antibiotic therapy administered every month,” study authors Clive Prestidge, Nicky Thomas, and PhD candidate Chelsea Thorn, said. “Our research successfully treats advanced human cell culture lung infections using nano-enhanced Tobramycin and shows how it can eradicate serious and persistent infections after only two doses. This could be a real game-changer for people living with CF.”

In the ACS Infectious Diseases paper, the study authors detailed their comparison of liposomes and the nanotech technology. In this case, the nanotech was loaded with Ps1G, the glycoside hydrolase, and Tobramycin to test if the combination would protect Ps1G from proteolysis, trigger the enzyme’s release in the presence of bacteria, and/or improve the total antimicrobial effect.

The study authors found that the nanotech approach was deemed to be an effective strategy that better protected against proteolysis, produced a sustained release of Ps1G, and improved the antimicrobial effect by 10-100-fold. Additionally, the study authors observed an increased survival of in vitro and in vivo Caenorhabditis elegans infected with P. aeruginosa.

When comparing digestible to non-digestible nanotech, the study authors determined that the digestible type triggered the enzyme’s release in the presence of bacteria. However, there were negligible differences in the versions’ ability to protect Ps1G from proteolysis and potentiate the antimicrobial activity when combined with Tobramycin.

They called the nanotech “a promising protective delivery system for novel biofilm dispensing enzymes combined with antibiotics,” in addition to infection-directed therapy and improved performance.

“Our technology improves the performance of Tobramycin without increasing the toxicity of the drug, so what we’re doing is a far more effective and efficient treatment for chronic lung infections,” the study authors added in the statement.