Minute drug delivery systems show promise of treating deep infections

Minute drug delivery systems show promise of treating deep infections

News Release Distributed 12/06/12

BATON ROUGE, La. – It may be the ultimate "silver bullet" – an extremely small particle made of iron coated with ceramic and silver and finally a powerful drug that can find its way through the human body to target a deep infection – and treat it.

A team of researchers in Louisiana are working together to develop a nanoscale drug delivery system that can target antibiotics to specific locations in the body.

Antibiotic drug resistance is considered one of the leading health care concerns in the world, according to Dan Hayes, an engineer in the LSU AgCenter Department of Biological and Agricultural Engineering. Reducing the antibiotics used can lessen the likelihood of drug resistance.

The system Hayes is working on targets antibiotics to hard-to-resolve infections associated with surgeries, particularly sites deep in the body associated with joint replacement and implants.

Hayes' specialty is designing the vehicle used to deliver the drugs.

The heart of the system is a delivery package that's part metal and part organic, Hayes said. It's composed of an iron core inside a ceramic shell covered by a silver coating. The whole thing then is covered with "targeting" drug molecules that seek out and attach to the bacteria that are causing an infection.

When a doctor identifies a short list of bacteria he suspects are causing specific infections, Hayes designs the package that includes the targeting drug.

"We use targeting molecules that have been identified to be attracted to particular bacteria," Hayes said. "It's a particle delivery system – when it hits the right bacteria, it sticks."

The process is particularly effective in finding and targeting bacteria in deep-tissue infections. The magnetic properties of the iron core allow an MRI to locate the infection.

The size of the package is extraordinary. It's measured in nanometers, which are one billionth of a meter. "One thousand nanoparticles arranged in a line would be about the diameter of a human hair," Hayes said.

The iron core is about 6 nanometers across, and by the time the ceramic and silver coatings are added, the particle can be about 50-60 nanometers across. Then the target molecules are added.

"Generally, the particle is about 70 nanometers across," Hayes said.

"We use light-scattering and metal analysis to 'look' at the particles," Hayes said. "We use electron microscopy and electric conductivity to generate a digital image."

Because they are smaller than cells, nanoparticles can move deep into tissues through the bloodstream and find their targets. The targeting compound can be easily changed, so the actual particle could be used to seek out many types of infection, he said.

Hayes fabricates and tests the nanoparticles in conjunction with the Pennington Biomedical Research Center in Baton Rouge and the LSU Health Sciences Center in New Orleans. Their primary targets are deep-tissue, antibiotic-resistant bacterial infections that commonly are associated with orthopedic implants.

The current process uses a unique steroid-based molecule that targets MRSA – Methicillin-resistant Staphylococcus aureus, a bacterial infection that is highly resistant to some antibiotics.

The coating part of the technology allows the antibacterial component to remain inert while it moves through the body. After it finds the infection, the doctors use an MRI to locate the nanoparticle because of the iron core. Then, once the drug reaches the infection, it can be activated by interaction with the bacteria or it can be triggered from outside the body using a laser. This allows patients to receive a higher dose of a drug that can act on the infection.

One of the challenges, Hayes said, is to ensure the nanoparticle can attract the antibacterial molecules, called aptamers, changing them. The targets don't have to be limited to MRSA, either. Other infections could be treated with different aptamers attached to the delivery system.

"This is particularly adaptable to orthopedics and implants now," Hayes said. "Better outcomes and fewer surgeries are the goals. This can give patients a quicker return to function and a better quality of life."

One of the advantages to working in the LSU AgCenter is the opportunity to collaborate with other researchers at Pennington and the LSU Life Sciences Center, Hayes said.

"By the normal process of the university, we were in the same place at the same time," he said. "Without the mandate to do research through public funding, this wouldn't have happened."

Rick Bogren

Last Updated: 12/6/2012 2:39:11 PM