Custom nanoparticle unlocks the anti-inflammatory potential of citrus

Scientists at the University of Alabama have developed a bio-engineered molecule that uses a natural compound to both target and treat inflammation.

Naringenin, a flavonoid found in citrus fruits, has long been recognized for its anti-inflammatory and antioxidant properties. However, our bodies do a poor job of absorbing the compound in the form of food or currently available supplements. Normally, naringenin starts to break down in the stomach’s acidic environment. The small amount left intact has trouble crossing the intestinal wall into the bloodstream. The UA team has successfully unlocked naringenin’s inflammation-fighting properties.

The study, published in Science Advances, uses a patented method of encasing medicine in a biodegradable polymer shell developed by UA’s Drug Research and Engineering for Advanced Medicine Laboratory. The outside of this shell is decorated with additional molecules of naringenin, functioning as ligands, that bind to specialized receptors found on cell surfaces throughout the gut.

The UA team found that naringenin is an effective ligand binder to a certain kind of receptor. These receptors are the gateways that allow the medicine in rather than locking it out.

“This is the first time a single molecule has been used to both guide and heal,” said Dr. Meenakshi Arora, an associate professor at UA and the project’s lead researcher. “Our dual-function nanoparticles not only deliver the drug more efficiently but also restore immune balance and reduce tissue damage.”

Promising results in kidney injury models

Using a mouse model with acute kidney injury induced by cisplatin, a common chemotherapy drug, the researchers demonstrated that their dual-function nanoparticles:

• Reduced kidney damage and inflammation.
• Lowered levels of key inflammatory markers.
• Restored immune cell function and reversed immune exhaustion.
• Achieved therapeutic effects at half the dose compared to conventional formulations.

Results suggest the treatment not only fights inflammation but actively promotes healing in both kidneys and liver. For cancer patients, this could mean fewer side effects and less recovery time needed between treatments, with a supplement they can take at home.

Almost all components of the dual-function naringenin particle are currently in human use, making it easier to navigate the regulatory path. The team is already working to test the particle against other health conditions, including cancer.

“One of the benefits of this system is that it is highly tunable,” said assistant professor Dr. Raghu Ganugula, the team’s molecular pharmacologist. “We can adjust it based on drug concentrations and ligand receptor interactions.”

The study’s findings have implications for a wide range of inflammatory conditions, including autoimmune disorders, sepsis, arthritis, and liver disease.

“Ultimately, this research provides a powerful proof-of-concept for a new class of oral drug delivery systems that could lead to more effective and lower-dose treatments for inflammatory diseases,” Arora said.

Why dosage matters

Third-year doctoral student Abiodun Wahab was responsible for managing the animal model part of the study. Wahab’s background in veterinary medicine gave her both the skills and a powerful motivation to explore safer dosing.

“When I was an undergraduate on a veterinary clinic rotation, I often treated parasitic infections,” she said.

The medicine often used to treat parasites was very effective but could be dangerous in the wrong dose.

“So I came here with the mindset that you have to be careful of the dose and the frequency of dosing,” Wahab said. “Learning about this innovative system in reducing drug concentration and toxicities was really important to me.”