A nanoparticle drug delivery system designed to shuttle molecules across the blood-brain barrier has shown promise in preclinical tests. The researchers used the system to transport siRNA across the intact blood-brain barriers of mice, pointing to its potential use in the treatment of traumatic brain injury (TBI).
TBI presents physicians with a short window lasting hours to days in which the blood-brain barrier is breached and therapeutic molecules can be delivered to the brain. Once the window closes, physicians are unable to get drugs to target tissues, preventing repeated dosing and limiting their ability to treat secondary injuries that can arise in TBI patients.
Researchers at Brigham and Women's Hospital and Boston Children's Hospital see nanoparticles as a solution to the drug delivery problem. The researchers published details of their work in the journal Science Advances.
The paper describes the modulation of surface coating chemistry and density to create nanoparticles capable of crossing the blood-brain barrier. By loading the optimized nanoparticles with siRNA and delivering them into mice, the researchers provided early validation of the potential of the approach.
Tau siRNA-loaded nanoparticles achieved up to 50% tau silencing in TBI mice. Tau was unaffected in mice treated with siRNA using a conventional delivery system. If translated into humans, the finding could support the long-term, noninvasive modulation of disease pathways in TBI patients. There is also scope to use the system beyond TBI.
“The technology developed for this publication could allow for the delivery of large number of diverse drugs, including antibiotics, antineoplastic agents, and neuropeptides. This could be a game changer for many diseases that manifest in the CNS,” Boston Children's Hospital’s Rebekah Mannix, M.D., said in a statement. The researchers are looking beyond tau for clinical translation.
Other groups are exploring protein- and peptide-based approaches to enhancing blood-brain barrier penetration. The authors of the Science Advances paper said the low cost, high stability and low immunogenicity of their approach give it advantages over other methods of getting drugs across the blood-brain barrier.