Scientists Develop Nanoparticle Drug Delivery Systems to Treat Brain Disorders

A team of bioengineers, doctors, and collaborators at Brigham and Women’s Hospital and Boston Children’s Hospital have created a nanoparticle platform for successful delivery of the drug to the brain. This results in a physically ruptured or intact blood-brain barrier (BBB).

Over the last few decades, researchers have identified biological pathways leading to neurodegenerative diseases and developed promising molecular agents to target them. However, the conversion of these findings to clinically approved treatments is much slower due to the challenges scientists face in delivering therapeutics to the brain across the blood-brain barrier (BBB). I am proceeding with.

In a mouse model of traumatic brain injury (TBI), we observed that the delivery system showed three times the intracerebral accumulation of traditional delivery methods, was therapeutically effective, and could open up therapeutic possibilities for many neuropathy. Did. The findings were published in Science Advances.

Previously developed approaches for delivering therapeutics to the brain after TBI rely on a short time frame after physical injury to the head when the BBB is temporarily ruptured. However, after the BBB has been repaired within a few weeks, doctors lack tools for effective drug delivery.

“It’s very difficult to deliver both small and high molecular weight therapeutics to the entire BBB,” said Nitin Joshi, a quasi-bioengineer at the Nanomedicine Center in Brigham’s anesthesiology, perioperative and pain medicine departments. The doctor said. “Our solution is to encapsulate the therapeutic agent in biocompatible nanoparticles with precisely designed surface properties that allow therapeutically effective transport to the brain, regardless of BBB status. It was to do. “

This technology enables physicians to treat secondary TBI-related injuries that can lead to Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases. These diseases can develop months to years after the BBB has healed.

“The ability to deliver the drug throughout the BBB without inflammation was a bit of a holy grail in this area,” said Dr. Jeff Carp, co-lead author of Brigham’s Anesthesiology, Perioperative and Pain Department. I will. medicine. “Our fundamentally simple approach can be applied to many neurological disorders where delivery of therapeutic agents to the brain is desired.”

Rebekah Mannix, MD, and MPH of the Department of Emergency Medicine at Boston Children’s Hospital, co-lead authors of the study, further emphasized that BBB broadly blocks the delivery of therapeutics to the central nervous system (CNS). Of acute and chronic illness. “The technology developed for this publication has the potential to enable delivery of a large variety of drugs, including antibiotics, antitumor drugs, and neuropeptides,” she said. “This can be a game changer for many diseases that occur in the central nervous system.”

The treatment used in this study was a small interfering RNA (siRNA) molecule designed to block the expression of tau protein, which is thought to play an important role in neurodegeneration. Poly (lactic-co-glycolic acid), or biodegradable and biocompatible polymers used in PLGA, some existing products approved by the US Food and Drug Administration, are used as the base material for nanoparticles. I did. Researchers have systematically designed and studied the surface properties of nanoparticles to maximize penetration of intact mice into the intact BBB. This identified a unique nanoparticle design that maximizes the transport of encapsulated siRNA through the intact BBB and significantly improves uptake by brain cells.

A 50% reduction in tau expression was observed in TBI mice that received anti-tau siRNA via a new delivery system, regardless of the formulation injected inside or outside the temporary window of the ruptured BBB. .. In contrast, tau was unaffected in mice that received siRNA via a traditional delivery system.

“In addition to demonstrating the usefulness of this new platform for drug delivery to the brain, this report utilizes systematic modulation of surface chemistry and coating densities to create tight junction biological barriers. For the first time, we will establish the ability to regulate the penetration of nanoparticles beyond. ” Dr. Wen Lee, lead author of anesthesiology, perioperative and pain medicine.

In addition to targeting tau, researchers are conducting research to attack alternative targets using the new delivery platform.

“For clinical translation, we want to go beyond tau and verify that our system is suitable for other targets,” Carp said. “We have explored and developed this technique using the TBI model, but anyone who is essentially studying neuropathy may find this job beneficial. Certainly I Our work has been cut out, but I think this will provide great momentum for us to move towards multiple therapeutic targets and we are in a position to move on to human testing. ”

(With input from ANI)

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