Tobramycin Nanoparticles are 10,000 fold more effective against Pseudomonas aeruginosa

Significance 

Novel nanotechnology developed by the University of South Australia could change the lives of thousands of people living with cystic fibrosis   as groundbreaking research shows it can improve the effectiveness of the CF antibiotic Tobramycin, increasing its efficacy by up to 100,000-fold. The new technology uses a biomimetic nanostructured material to augment Tobramycin, the antibiotic prescribed to treat chronic Pseudomonas aeruginosa lung infections in severe cases of CF, eradicating the infection in as little as two doses.

Cystic fibrosis affects one in 2500 babies, or one baby born every four days causing severe impairments to a person’s lungs, airways and digestive system, trapping bacteria and leading to recurrent infections. Lung failure is the major cause of death for people with cystic fibrosis . According to the UniSA research team, which includes Professor Clive Prestidge, Dr Nicky Thomas, and PhD candidate, Chelsea Thorn the discovery could transform the lives of people living with cystic fibrosis .

Cystic fibrosis  is a progressive, genetic disease that causes persistent, chronic lung infections and limits a person’s ability to breathe. The disease causes thick, sticky mucus to clog a person’s airways, attracting germs and bacteria, such as Pseudomonas aeruginosa, which leads to recurring infections and blockages.

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.

The authors 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 cystic fibrosis .

Researchers enhanced the Tobramycin with a biometric, nanostructured, lipid liquid crystal nanoparticle (LCNP)-based material, testing it on a new lung infection model to showcase its unique ability to penetrate the dense surface of the bacteria and kill the infection. Tobramycin works by inhibiting the synthesis of bacteria and causing cell membrane damage. Yet, as it’s a concentration-dependent antibiotic, achieving a sufficiently high concentration is critical. 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 technology is currently entering pre-clinical trials and hopes to be on the market in the next five years.

New Tobramycin Nanoparticles formulation has 10,000 fold more effective against Pseudomonas aeruginosa - Medicine Innovates

About the author

Dr Nicky Thomas

Nicky Thomas is a Senior Research Fellow at UniSA’s Clinical and Health Sciences and The Basil Hetzel Institute for Translational Health Research.

The global theme of Nicky’s research is to transform new and existing drugs into the best medicines for patients. Nicky’s research is in particular concerned with the interaction of nanomedicines with bacterial biofilms and with the development of novel strategies to combat some of the most debilitating diseases – chronic infections. His second research interest is concerned with the question how nanomedicines can be used to improve the efficacy and safety of drugs with pharmaceutically challenging properties (e.g. poor water solubility, permeabilty, high toxicity such as cancer drugs). A trained pharmacist Nicky received his BSc in Germany (Albert -Ludwigs University, Freiburg). With several years of experience in community pharmacies, hospital pharmacies, and pharmaceutical industry he has specialised in the topical and oral delivery of drugs.

In 2012 Nicky obtained his PhD with distinction in Pharmaceutical Sciences from the University of Otago, New Zealand. His PhD research was concerned with the fate of lipid-based drug delivery systems and concomitantly administered drugs during digestion in the body. Following one year as a Postdoc at the University of Copenhagen, Denmark, he joined UniSA in 2013.

In 2014 Nicky was awarded a prestigious Australian National Health and Medical Research Council (NHMRC) Early Career Researcher Fellowship, and a Mid Career Fellowship from The Hospital Research Foundation in 2018.

Nicky is the founder and head of Adelaide’s first Biofilm Test Facility at UniSA. The facility offers academia, health care providers and industry a range of in vitro and in vivo efficacy tests for compounds, formulations and medical devices against biofilms that are associated with recurring and difficult to treat chronic infections.

Reference

Chelsea R. Thorn, Cristiane de Souza Carvalho‐Wodarz, Justus C. Horstmann, Claus‐Michael Lehr, Clive A. Prestidge, Nicky Thomas. Tobramycin Liquid Crystal Nanoparticles Eradicate Cystic FibrosisRelated Pseudomonas aeruginosa Biofilms. Small, 2021; 2100531 DOI: 10.1002/smll.202100531

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