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Way Found to Use Antimicrobial Peptides, Part of Immune System, to Treat Bacterial Lung and Wound In

Antimicrobial peptides administered as tiny nanoparticles show promise in treating bacterial infections without risking making the bacteria more resistant to treatment — as can happen with antibiotics, an EU-supported study reports.

Unlike antibiotics, antimicrobial peptides or AMPs are part of the innate immune system, naturally occurring molecules that work as the body’s first-line of defense against threats like bacteria.

But past attempts to use antimicrobial peptides failed to mostly due to their lack of stability, leading them to degrade quickly. Now, researchers found that using nanoparticles as a vehicle to deliver these small molecules directly to an infection site significantly improved their stability, keeping them from degrading, allowing AMPs to be more effective killing agents.

This finding is of particular importance to cystic fibrosis patients, as the researchers showed that nanoparticles with AMPs can ably penetrate bacterial biofilms that also make these infections resistant to treatment.

“Most conventional antibiotics are delivered through pills or injections, and if they underperform then more are prescribed. We have focused on treating skin and lung infection locally, thereby reducing exposure and making treatment easier for the patient,” Lovisa Ringstad, project coordinator at RISE (Research Institutes of Sweden), said in a news release.

AMPs can rapidly attack many different strains of bacteria, killing them by destroying their enclosing membrane. Unlike common antibiotics, they are less prone to triggering resistance in infectious bacteria, making them attractive therapeutic candidates to fight infections.

However, their use has been limited by their tendency to degrade quickly while in storage and during treatment. The researchers’ challenge was to find ways to deliver fully active AMPs to infection sites.

The preclinical FORMAMP project focused on developing nanotechnology-based carriers to deliver AMPs directly to infected tissue as proof-of-concept.

“FORMAMP showed that structured nanoparticles are efficient delivery vehicles for a range of antimicrobial peptides needed for effective therapy,” Ringstad said.

Researchers working in the laboratory tested several types of nanoparticles — porous silica particles, liquid crystalline nanoparticles, and star-shaped macromolecules — and assessed their ability to absorb, protect, and release AMPs with minimal toxicity.

The selected nanoparticles were evaluated as potential treatments for skin wounds and lung infections.

“One important result concerned the effect of nanoparticles on biofilms,” Ringstad said. “Biofilms are aggregations of infectious bacteria which protect the infected area against antibiotics and other therapies — they are common in many types of infection and are difficult to penetrate. We found that when nanoparticles are loaded with AMPs then the degradation of the biofilm was significantly improved.

“This ability to successfully attack biofilms is a very significant result for treating conditions such as cystic fibrosis and burn wound infections,” she said.

Nanoparticles used as a local delivery method can also “be more cost-effective, as they use less of the active ingredient, and have fewer side effects for the same reason,” Ringstad added.

Because they can be loaded with a range of treatments, they may also be a delivery vehicle for more effectively treating patients with various diseases, Ringstad concluded, noting that further research is necessary.

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