Antibiotic Nanoparticles Target Drug-Resistant Bacteria

Pharmaceutical Technology Editors

New study shows that an antimicrobial peptide packaged in a silicon nanoparticle significantly reduced bacteria load in the lungs of mice infected with Pseudomonas aeruginosa.

Scientist from MIT and other research groups are investigating the potential of using nanoparticles to target drug-resistant bacteria. A new study showed that an antimicrobial peptide packaged in a silicon nanoparticle significantly reduced bacteria load in the lungs of mice infected with Pseudomonas aeruginosa, the strain responsible for causing pneumonia. It is believed that this approach can be applied to the treatment of other bacterial infections such as tuberculosis. It is based on the same concept of targeted drug delivery for anticancer therapeutics.

“There are a lot of similarities in the delivery challenges. In infection, as in cancer, the name of the game is selectively killing something, using a drug that has potential side effects,” Sangeeta Bhatia, senior author of the study, commented in a press release.

Antimicrobial peptides are naturally occurring defensive proteins disrupts cellular targets of the bacteria, such as membranes and proteins, or cellular processes such as protein synthesis. Researchers are exploring how antimicrobial peptides can be used in the fight against antibiotic resistance. Bhatia and her colleagues investigated the possibility of using nanoparticles for targeted delivery of antimicrobial peptides. They combined an antimicrobial peptide with another peptide that would help the drug cross bacterial membranes. This concept was built on previous work suggesting that these “tandem peptides” could kill cancer cells effectively.

For the antimicrobial peptide, the researchers chose a synthetic bacterial toxin called KLAKAK. This toxin was attached to a variety of “trafficking peptides,” which interact with bacterial membranes. Twenty-five tandem peptides were tested, and the best one turned out to be a combination of KLAKAK and a peptide called lactoferrin, which was 30 times more effective at killing Pseudomonas aeruginosa than the individual peptides were on their own. It also had minimal toxic effects on human cells.

The researchers decided to package the peptides into silicon nanoparticles to further minimize potential side effects. The nanoparticles are believed to prevent the peptides from being released too soon and damaging other tissues before reaching the targets. In this study, the researchers delivered the particles directly into the trachea of mice. An inhaled version will be developed for human use.

After the nanoparticles were delivered to infected mice, it was observed that those mice had approximately one-millionth the number of bacteria in their lungs as untreated mice, and they survived longer. The researchers also found that the peptides could kill strains of drug-resistant Pseudomonas taken from patients and grown in the lab.

Bhatia’s research group is currently working on incorporating another peptide that would help target antimicrobial peptides to a specific location in the body. Another project involves using trafficking peptides to help existing antibiotics that kill Gram-positive bacteria to cross the double membrane of Gram-negative bacteria, enabling them to kill those bacteria as well.

Source: MIT