Researchers breach brain-blood barrier, deliver medicine precisely via nanoparticles
Science & Technology | World: People with cachexia lose weight even if they eat. The debilitating syndrome affects up to 80% of advanced cancer patients and kills as many as 30% of the cancer patients it afflicts.
Researchers have finally found a way to breach the blood-brain barrier and deliver anti-inflammatory medicine across in a huge development that opens the door to potential treatments for a range of serious neurological conditions like Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and cancer cachexia.
Oregon State University researchers found a way to get anti-inflammatory medicine across the blood-brain barrier by using specially engineered nanoparticles, tiny bits about 100 billionths of a metre.
The team deployed the dual peptide-functionalised polymeric nanocarriers and delivered a drug that inhibits a key protein associated with inflammation to the intended destination, the hypothalamus of the brain, in a mouse model, said a ScienceDaily report.
Also Read | Now a simple blood test could detect Parkinson’s disease long before symptoms emerge
“Our work presents a significant breakthrough,” said Oleh Taratula, professor in the OSU College of Pharmacy.
The findings were published in Advanced Healthcare Materials on April 9.
The hypothalamus is a vital part of the brain just below the thalamus and above the brainstem and helps maintain homeostasis—the body’s internal balance. It regulates the body temperature, manages sleep cycles, hormone production, and emotional responses, besides controlling hunger and thirst.
In the study, researchers specifically looked at the hypothalamus as it is linked to cachexia, a metabolic syndrome that leads to involuntary weight loss and muscle wasting, often 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 cachexia lose weight even if they eat. 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.”
The systemic delivery of anti-inflammatory agents, including the IRAK4 inhibitors used in this research, to the hypothalamus presents significant challenges, mainly because of the restrictive nature of the blood-brain barrier, Taratula added.
Also Read |Russia seeking to deploy nuclear weapons in space, warns NATO chief
The blood-brain barrier, often called BBB, is a protective shield separating the brain from the bloodstream to protect it. It 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, allowing nutrients like oxygen and glucose to pass through while blocking toxins and pathogens, keeping the brain safe from infections and damage. But in this role, it also denies 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,” he said, adding, “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 results were promising as the team observed substantial reductions in key inflammatory markers in the hypothalamus, which led to a 94% increase in food intake and significantly preserved body weight and muscle mass.
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 characterised by brain inflammation, including Alzheimer’s disease and multiple sclerosis,” he said.
In the study, Taratula was joined 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.
