Can nanoparticles be used for antibacterial purposes?

21 August 2020, 14:26

Decades of misuse of antibiotics has led to the number of bacteria resistant to commercially available antibiotics is increasing worldwide and this is one of the major challenges facing global health according to WHO. Antimicrobial peptides are host defense peptides present as part of the innate immune system in virtually all life forms and these are being considered a potential treatment for bacterial infections. Maja Hellsing and her team at RISE have studied nanoparticles combined with LL-37 antimicrobial peptides using neutron reflectometry at the ISIS Neutron and Muon source.

LL-37 are important antimicrobial peptides found in humans and recent studies have shown that this peptide can be incorporated into cubic liquid crystalline nanoparticles known as cubosomes. The well-organised internal structure of cubosomes consists of alternating hydrophilic and hydrophobic domains means they are compatible with both water soluble, insoluble and amphipathic molecules.

Cubosomes have already shown great promise as a delivery system for pharmaceuticals. This unique drug-delivery system has in this work been tested in vitro to understand its effect on bacteria. The cubosomes are able to protect LL-37 from enzymatic degradation by human and bacterial elastases, which has previously limited LL-37 therapeutic use. However, the bactericidal mechanisms of cubosomes loaded with LL-37 is not fully understood.

The bacterial membrane disruptive properties of the LL-37 loaded cubosomes was studied using neutron reflectometry. This technique is available at ISIS Neutron and Muon source (Rutherford Appleton Laboratory, Didcot, U.K.) and was in this work carried out on the CRISP reflectometer using custom-made sample holders. The aim was to investigate the interaction between LL-37 loaded cubosomes with a bacteria mimicking model membrane lipid bilayer to resolve the bacterial killing mechanism of the drug loaded particles as compared to pure peptide. By using a labelled (deuterated) lipid bilayer, the disruption of the bilayer can be visualized to investigate if there is a difference between the LL-37 loaded particles and pure peptide. The neutron reflection experiments provide the opportunity to differentiate between peptide adsorption to the bilayer, peptide loaded particles adsorbing or no absorption but with removal of lipids, which cannot directly be monitored using other techniques.

The findings of this research suggest that LL-37 loaded cubosomes form an antibacterial unit, potentially altering gram-negative bacteria in a lethal way, whilst protecting the LL-37 from enzymatic degradation. Although further in vivo studies are needed to evaluate the clinical relevance of cubosomes as a drug delivery system, the results from this study suggest that the cubosome-bacteria interaction is of a significant importance for the killing of bacteria and the antibiotic crisis.

The work was done in a collaboration between researchers at RISE Research Institutes of Sweden, Lund University, University of Copenhagen, Uppsala University, Chalmers University of Technology and ISIS Neutron and Muon Source.