New Delivery Method Paves the Way for Anti-Inflammatory Treatments in Brain Diseases: Study - Video

Oregon State University researchers have discovered a way to get anti-inflammatory medicine across the blood-brain barrier, opening the door to potential new therapies for a range of conditions, including Alzheimer’s disease, multiple sclerosis, Parkinson’s disease and cancer cachexia. Findings were published today in Advanced Healthcare Materials.

The delivery method involves specially engineered nanoparticles, tiny bits of matter no larger than 100 billionths of a meter. Tested in a mouse model, the dual peptide-functionalized polymeric nanocarriers reached their intended destination, the hypothalamus, and delivered a drug that inhibits a key protein associated with inflammation.

People with cancer cachexia will lose weight even if they eat, and not just fat but muscle mass as well. The debilitating syndrome affects up to 80% of advanced cancer patients and kills as many as 30% of the cancer patients it afflicts.

The systemic delivery of anti-inflammatory agents, including the IRAK4 inhibitors used in this research, to the hypothalamus presents significant challenges, Taratula said, mainly because of the restrictive nature of the blood-brain barrier.

“An additional hurdle, even if you can get through the BBB to the hypothalamus, is hitting the bullseye within the hypothalamus – the activated microglia cells that act as key mediators of inflammation,” said Oleh Taratula, professor in the OSU College of Pharmacy. “Our nanocarriers show a dual-targeting capability, and once in the microglia, drug release is triggered by elevated intracellular glutathione levels. We demonstrated, for the first time, that nanocarriers can successfully deliver an IRAK4 inhibitor to the hypothalamus of mice with cancer cachexia.”

The scientists observed substantial reductions in key inflammatory markers in the hypothalamus, and the nanocarriers led to a 94% increase in food intake and significantly preserved body weight and muscle mass. And the implications extend far beyond cancer cachexia, Taratula added.

Reference: Goo, Y. T., Grigoriev, V., Korzun, T., Sharma, K. S., Singh, P., Taratula, O. R., ... & Taratula, O. Blood‐Brain Barrier‐Penetrating Nanocarriers Enable Microglial‐Specific Drug Delivery in Hypothalamic Neuroinflammation. Advanced Healthcare Materials, 2500521.