BBB Pathophysiology-Independent Drug Delivery in Traumatic Brain Injury

3/16/2021 09:30 - 10:05

Over past few decades, researchers have identified several promising therapeutic agents that can mitigate the long-term sequelae of traumatic brain injury (TBI). However, their clinical translation has been limited due to poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while the BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We have developed a nanoparticle platform for BBB pathophysiology–independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing. Together, our data suggest that this nanoparticle platform is a promising next-generation drug delivery approach for the treatment of TBI.

Nitin Joshi, Instructor of Anesthesia, Center for Nanomedicine, Brigham and Women’s Hospital, Harvard Medical School