For many years, researchers have dreamed of creating new medicines using the human body’s own peptides against viral and bacterial infections. Nanogels may be the key to enabling this.
Antibiotics are losing their punch, and new bacterial strains are becoming resistant. Further, we lack effective antiviral drugs, as was evident during COVID-19, so researchers are looking for entirely new ways to fight infections.
In both respects, researchers have been examining antimicrobial peptides for a long time. These tiny protein fragments can kill bacteria and viruses by rupturing their membranes or disturbing their vital machinery.
Because peptides are found naturally in the human body, there is less risk of microbes developing resistance. They are also kinder to human cells.
However, antimicrobial peptides have yet to make their breakthrough – partly because they are quickly broken down by the body’s enzymes and flushed out before they can take effect.
The solution may be to wrap the peptides in soft, invisible jelly beads – nanogels – which protect them and make them linger longer precisely where the infection strikes.
“Before we can realise the potential of antimicrobial peptides, we need to find a way to control them. For example, they have a very short lifespan, which means that the effect in the body is very brief. With this study, we show that there is potential in encapsulating the peptides in a nanogel to extend their lifetime without losing their antimicrobial effect,” explains a researcher behind the study, Hanne Mørck Nielsen, Professor at the Department of Pharmacy of the University of Copenhagen, Denmark.
Soft capsules keep infection-fighting peptides active longer
For example, imagine wanting to cure pneumonia with antimicrobial peptides. As things stand today, you can try to inhale the peptides, but that will not do much for the pneumonia because of the short lifespan of the peptides.
To solve this, Hanne Mørck Nielsen and her colleagues designed a hyaluronic acid nanogel to encapsulate the peptides.
Hyaluronic acid is a polymer that occurs naturally in the body and as such is not dangerous to humans, and it is biodegradable and is excreted from the body.
The researchers developed the polymer to form small capsules that can contain bioactive molecules, including peptides.
The idea behind encapsulating the peptides in the hyaluronic acid polymer is that it reduces the rate at which the peptides are broken down – so they can be effective for longer: for example, in the lungs.
“In the laboratory, we have tested how the peptides work on cells. When encapsulated in nanogels, they work just as well – and are even gentler on the human cells we are trying to protect,” says Hanne Mørck Nielsen.
She adds that previous studies have also indicated that the nanogel capsules diffuse better into the mucus layers in the respiratory tract or, for that matter, in the gut.
“This is interesting because bacteria often live in the mucus layers and form biofilms, making them difficult to reach. This means that the nanogels may be able to penetrate the slimy layers where the bacteria hide – and hit them where antibiotics normally have difficulty reaching,” adds Hanne Mørck Nielsen.
Nanogels extend treatment time in the lungs
The researchers tested the nanogels in mice for the first time – a crucial step in finding out how the substance acts in a living body and whether it can become a real medicine.
Together with collaborators at the University of British Columbia, the researchers labelled both the antimicrobial peptides (peptide LL37) and the nanogels with separate radioactive isotopes so they could use a sophisticated scanner (single photon emission computed tomography (SPECT) in combination with computed tomography (CT)) to track exactly where the peptides and nanogels moved around the body.
“By scanning the whole animal, we can track how much of the peptide and nanogels remain in the lungs and how much are excreted from the kidneys, for example. We can follow this over time,” explains Hanne Mørck Nielsen.
The study showed that the peptides are slowly released from the nanogels and that they disappear from the lungs faster than the nanogels do.
However, the antimicrobial peptides remain in the lungs for longer than they would otherwise.
Without nanogels, 85% of the peptides vanished from the lungs within 48 hours. With nanogels, they stayed up to 36% longer – long enough to have effect before being cleared by the body.
Longer-lasting effect and lower risk of side-effects
Hanne Mørck Nielsen suspects that the reason is that the peptides are retained in the mucus layer of the lungs for longer with the help of the nanogels.
In addition, the researchers also found that the concentration of the peptide in the kidneys decreased, which is good because it minimises the risk of toxic effects there.
“We found a significant effect of encapsulating antimicrobial peptides in our nanogel. It makes them stay in the lungs for longer without increasing the toxic effect. Further, we can conclude that both peptides and our polymer can be labelled with a radioactive isotope so we can follow them over time. The results suggest that nanogels could be the missing link in turning antimicrobial peptides into real-world medicines. This is a promising step toward new resistance-proof therapies for the infections of tomorrow,” says Hanne Mørck Nielsen.
She envisions future medicinal solutions in which nanogels containing antimicrobial peptides are inhaled with an inhaler and that they then settle in the mucus layer and affect the bacteria there.
