Reviewed by Lexie CornerApr 10 2025
Researchers from Oregon State University have developed a method to deliver anti-inflammatory drugs across the blood-brain barrier, which may enable new treatments for diseases such as cancer cachexia, multiple sclerosis, Parkinson’s disease, and Alzheimer's disease.
Nanocarriers crossing the blood-brain barrier. Image Credit: Tetiana Korzun
The delivery system uses specially designed nanoparticles, which are small particles no larger than 100 billionths of a meter.
In a mouse model, the dual peptide-functionalized polymeric nanocarriers successfully reached their target, the hypothalamus, and delivered a drug that inhibits a key protein involved in inflammation.
Our work presents a significant breakthrough.
Oleh Taratula, Professor, Oregon State University
The hypothalamus is a small but crucial part of the brain, located below the thalamus and above the brainstem. It is responsible for maintaining homeostasis. It regulates functions such as temperature, sleep cycles, hormone production, emotional responses, hunger, and thirst.
In this study, researchers focused on the hypothalamus in relation to cachexia, a severe weight-loss condition associated with cancers of the ovaries, stomach, lungs, and pancreas, as well as other chronic conditions like renal failure, cystic fibrosis, Crohn’s disease, rheumatoid arthritis, and HIV.
Cancer cachexia causes individuals to lose weight, including both fat and muscle mass, even if they continue to eat. This syndrome contributes to the death of up to 30 % of cancer patients and affects up to 80 % of those with advanced disease.
“Inflammation of the hypothalamus plays a pivotal role in dysregulating those patients’ appetite and metabolism. As cachexia progresses, it significantly impacts quality of life, treatment tolerance, and overall survival chances,” Taratula added.
According to Taratula, the blood-brain barrier (BBB) presents a significant challenge in delivering anti-inflammatory drugs, such as IRAK4 inhibitors used in this study, to the hypothalamus.
The BBB is a protective barrier that separates the brain and bloodstream. It regulates the movement of substances between the blood and the brain, consisting of tightly packed cells that line the blood vessels in the brain.
This barrier protects the brain from infections and damage by allowing essential nutrients like oxygen and glucose to pass through while blocking harmful substances like toxins and pathogens. However, it also restricts the entry of therapeutic agents.
Taratula explained further, “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. 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 research demonstrated that the nanocarriers resulted in a 94 % increase in food intake and significant preservation of body weight and muscle mass. Additionally, key inflammatory markers in the hypothalamus were significantly reduced. Taratula noted that these results extend beyond cancer cachexia.
“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 added.
The study team included Daniel Marks from Endevica Bio, along with Yoon Tae Goo, Vladislav Grigoriev, Tetiana Korzun, Kongbrailatpam Shitaljit Sharma, Prem Singh, and Olena Taratula from the College of Pharmacy.
The study was funded by the National Research Foundation of Korea, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Cancer Institute of the National Institutes of Health.