Antibiotic nanoparticles attack respiratory infection at source and reduce drug side-effects

13-Mar-2015

Drugs to treat respiratory disease need to be given in large quantities for an effective amount to reach the target

Treating respiratory disease is often difficult: drugs must cross biological barriers (respiratory tissue and mucosa) and need to be given in large quantities for an effective amount to reach the target. New research from Germany, Brazil and France has shown that the use of nanoparticles to carry antibiotics across biological barriers can be an effective way to treat lung infections.

Doing so allows better delivery of the drug to the site of infection, preventing the development of antibiotic resistance that may result from the overuse of antibiotics. Additionally, such a strategy might help to overcome the rapid metabolism and excretion of antibiotics from the body, which happens when traditional administration routes (oral or intravenous) are used.

Describing her team’s work to the 13th European Respiratory Society Lung Science Conference in Estoril, Dr Cristiane Carvalho-Wodarz, from the Helmholtz Institute for Pharmaceutical Research (Saarbrücken, Germany), says: By developing nanoparticles loaded with clarithromycin, an antibiotic commonly used in the treatment of respiratory infections, we have been able to mimic the process that occurs after inhalation in vivo by delivering the drug through aerosol deposition to lung cells.

‘Nanoparticles, which are in the same size range as a virus, were prepared by adding a biodegradable polymer oil, stabiliser and clarithromycin dissolved in solvents, to an aqueous surfactant solution. Subsequently, the solvents were completely removed. The delivery of nanoparticles in this way enables their deposition in cells cultivated in vitro in a similar way to the deposition in vivo, which takes place in the alveoli.’

The researchers used the bacterium Staphylococcus aureus as the model for their experiment, as it is one of the major causes of hospital-acquired infection and also plays a crucial role in the lung infections that are common in the genetic disorder cystic fibrosis. The tiny clarithromycin nanoparticles (CLARI-NPs), were able to access the bacteria located either in biofilms or inside individual lung cells.

‘Neither of these locations is conducive to effective drug delivery through traditional routes,’ says Dr Carvalho-Wodarz, ‘so we were pleased to see that not only did the use of CLARI-NPs allow the uptake of the antibiotic by the lung cells, but also that there were no toxic effects on all the cell types on which we tested.’

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To date, the work has been in vitro, using human bronchial cells. The researchers now hope to evaluate its effectiveness in an animal model. They would also like to test the same nanoparticles loaded with other drugs used against lung infections, and in particular those in which the infectious agent becomes drug-resistant after the continued large doses that may be required.

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