NIH grant awarded to Sharma to study a new two-pronged drug delivery strategy for treatment of osteoarthritis

Osteoarthritis, or OA, is a complex disease marked by several harmful processes within the joint, such as cartilage damage and inflammation of the joint cavity’s inner lining. Current clinical options aim to address pain rather than these OA processes, which only prolongs inevitable joint destruction that leaves many patients requiring total joint replacement.

A new $1.57 million grant from the National Institutes of Health will aid Dr. Blanka Sharma, assistant professor in the J. Crayton Pruitt Family Department of Biomedical Engineering, and her collaborators Dr. Kyle Allen, BME associate professor, and Dr. Wendy Liu, associate professor of biomedical engineering at UC Irvine, in developing a new drug delivery system to protect joint cartilage and reduce inflammation.

“There is a need for essentially different types of drugs in different locations within the joint,” Sharma said.

During OA progression, cells within the joint die, including chondrocytes, which produce and maintain cartilage. Kartogenin, a drug that has been shown to protect these cells, will be delivered to the cartilage as part of this study. Another molecule that will be introduced to the joint is CD200, which has been found to steer immune cells towards anti-inflammatory behavior.

Although there has been progress in identifying drugs for OA, clinical translation has not yet been achieved. This lack of success stems from the rapid clearance of drugs from the body, resulting in the need for frequent injections, but other challenges due to localization of drugs have been problematic.

“We don’t just need (the drug) to be retained...we need it to get to the right tissue because there are promising chondroprotective or cartilage regenerating molecules, but they have really serious off-target effects (within the joint),” Sharma said.

In order to overcome these challenges and localize drugs to their target tissues, Sharma aims to deliver drugs with micro- and nano-size particles made from biocompatible polymers.

Nanoparticles small enough to penetrate into the cartilage tissue will be loaded with kartogenin and “painted” directly onto the cartilage with a sealant, Sharma said. To avoid clearance, these particles have been designed to anchor themselves by binding to molecules found within the cartilage.

For anti-inflammation, CD200-coated microparticles large enough to limit their clearance will be injected directly into the joint cavity, Sharma said.

These two methods will be studied in preclinical OA models both separately and in combination to reveal whether simultaneous delivery can impact OA more than either of the treatments alone. Data from these experiments will be analyzed by studying both joint tissue and behavioral changes.

This new delivery approach could advance the field of targeted delivery in the joint by opening the door for previously ineffective drugs to reach their target tissues.

“With the right delivery systems and approaches, you could enable certain therapies that on their own, just as a drug alone, might never be clinically viable, because of, say, off-target effects or poor retention,” Sharma said.

These studies might also reveal important OA processes. Findings could give insight regarding how immune cell behavior and cartilage protection affect OA progression, which could help researchers inch closer to a cure for OA, Sharma said. 

By Jonathan Griffin, BME Ph.D. student