Cystic fibrosis is a life-threatening genetic disease which affects lung function through the build-up of a difficult to clear mucus. This occurs due to a gene mutation, and the mucus which builds up is an ideal environment for bacterial infections, which cause inflammation and structural damage to the lungs.

Delivery of antibiotics is crucial to treating the disease, and the implementation of inhalers for drug delivery has optimised drug delivery direct to the source of the mucus build-up. This being said, the delivered drugs struggle to penetrate through the thick mucus, and therefore do not have full efficacy.

One research group from the Jordan University of Science and Technology have developed a drug delivery technique which may allow for patient antibiotics to penetrate through the mucus barrier and have full effect on treating bacterial infection.

This is through use of nanoparticles which are able to penetrate the thick mucus layers, loaded with tobramycin (a commonly prescribed antibiotic for cystic fibrosis patients), that is released over time as the nanoparticle degrades to produce a sustained and controlled dosing of antibiotics.

In addition to this, the nanoparticle is covered in chitosan, which can attach to mucus and ensure that the drug loaded nanoparticle is present at the site of infection.

Antimicrobial And Biofilm Eradicating

The researchers found that use of all different nanoparticle formulations performed significantly better at producing an antimicrobial and biofilm eradicating effect – a step which helps bacterial infections stick to a surface – compared to tobramycin alone.

The control nanoparticles used for this study had no tobramycin encapsulated within them, and had no effect on bacteria or biofilm production; exhibiting that all of the bacterial effects were related to the presence of the antiobiotic, which was enhanced by the presence of the nanoparticle formulation.

The physical surface chemistry of the nanoparticles also allowed for better adhesion to the mucus of the lungs. In addition the physical chemistry of the nanoparticle polymers in conjunction with the chitosan coating allowed for a sustained release of tobramycin over time.

[caption id=“attachment_94764” align=“aligncenter” width=“680”]Scanning electron microscope images of LMWC-PLGA nanoparticles showed nanosized spherical particles Scanning electron microscope images of LMWC-PLGA nanoparticles showed nanosized spherical particles
Credit: Nusaiba K. Al-Nemrawi et al. CC-BY[/caption]

The combination of drugs and nanoparticles are a very attractive prospect for enhancing the delivery of therapeutics for many different diseases. The sustained release of antibiotic exhibited in this study is extremely useful for treating diseases like cystic fibrosis, where continued dosage of drug enhances treatment effects.

In addition, the ability to tailor the physical parameters of a nanoparticle formulation for a certain purpose, for example for enhanced mucus adherence and penetration in this cystic fibrosis, or for increased blood-brain barrier penetrance for a range of neurodegenerative diseases, could reap significant therapeutic benefits.

Al-Nemrawi, N.K.; Alshraiedeh, N.H.; Zayed, A.L.; Altaani, B.M. Low Molecular Weight Chitosan-Coated PLGA Nanoparticles for Pulmonary Delivery of Tobramycin for Cystic Fibrosis Pharmaceuticals. 8 March 2018. doi:10.3390/ph11010028

Author: Geoffrey Potjewyd; Regenerative Medicine & Neuroscience PhD student at the University of Manchester. Image: Electrospun chitosan fiber strand. Credit: msaustero Flickr.

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