OSU scientists created nanoparticles that deliver anti-inflammatory drugs across the blood-brain barrier, offering hope for treating cachexia and brain-related diseases.
Researchers at Oregon State University have developed a method to deliver anti-inflammatory drugs across the blood-brain barrier, a breakthrough that could lead to new treatments for conditions such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and cancer-related cachexia.
The approach uses specially engineered nanoparticles, extremely small particles measuring less than 100 nanometers in size.
In mouse model testing, these dual peptide-functionalized polymeric nanocarriers successfully targeted the hypothalamus and delivered a drug that blocks a key protein involved in inflammation.
“Our work presents a significant breakthrough,” said Oleh Taratula, professor in the OSU College of Pharmacy.
The findings were published in the journal Advanced Healthcare Materials.
Understanding the Hypothalamus and Cachexia
The hypothalamus is a small but vital part of the brain situated below the thalamus and above the brainstem, and it plays a key role in maintaining homeostasis – the body’s internal balance. It regulates body temperature, manages sleep cycles, hormone production, and emotional responses, and controls hunger and thirst.
In this study, researchers specifically looked at the hypothalamus as it pertains to cachexia, a deadly weight-loss condition associated with cancers of the ovaries, stomach, lungs, and pancreas and other chronic conditions such as renal failure, cystic fibrosis, Crohn’s disease, rheumatoid arthritis, and HIV.
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.
“Inflammation of the hypothalamus plays a pivotal role in dysregulating those patients’ appetite and metabolism,” Taratula said. “As cachexia progresses, it significantly impacts quality of life, treatment tolerance, and overall survival chances.”
Overcoming the Blood-Brain Barrier
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.
The blood-brain barrier, often referred to as the BBB, is a protective shield separating the brain from the bloodstream. The BBB is made up of tightly packed cells lining the blood vessels in the brain and controls what substances can move from the blood to the brain.
It allows essential nutrients like oxygen and glucose to pass through and blocks harmful substances such as toxins and pathogens, keeping the brain safe from infections and damage. But it can also deny entry to therapeutic agents.
“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,” Taratula said. “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.
“The nanoplatform’s ability to deliver therapeutics across the BBB and target microglia opens new possibilities for treating neurological conditions characterized by brain inflammation, including Alzheimer’s disease and multiple sclerosis,” he said.
Reference: “Blood-Brain Barrier-Penetrating Nanocarriers Enable Microglial-Specific Drug Delivery in Hypothalamic Neuroinflammation” by Yoon Tae Goo, Vladislav Grigoriev, Tetiana Korzun, Kongbrailatpam Shitaljit Sharma, Prem Singh, Olena R. Taratula, Daniel L. Marks and Oleh Taratula, 3 April 2025, Advanced Healthcare Materials.
DOI: 10.1002/adhm.202500521
Taratula was joined in the study by College of Pharmacy colleagues Yoon Tae Goo, Vladislav Grigoriev, Tetiana Korzun, Kongbrailatpam Shitaljit Sharma, Prem Singh and Olena Taratula, and by Daniel Marks from Endevica Bio.
The National Cancer Institute of the National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Research Foundation of Korea funded the research.
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.