Nanoparticle (NP)-based systems have recently gained significant traction and NP applications for brain disorders, specifically traumatic brain injuries (TBI) are limited by the complex pathology including blood-brain barrier (BBB) disruption. Previously, we have established in both focal and diffuse injury models of TBI that 20-500 nm NPs accumulate within the injury region out to 24h post-injury correlating with BBB disruption
. Seminal TBI studies in male rodents suggest a biphasic BBB opening with the first peak at acute (~3-6h) time point followed by a delayed opening (~3d) after TBI
. Therefore, the first objective of this study aimed to characterize extended NP delivery outside of 24hr post-injury. Secondly, sex is known to play a role in the morbidity and mortality after TBI, yet the underlying mechanisms are not well elucidated. Early sex-specific studies reported decrease BBB disruption in female rodents compared to the males within the first 6h following injury
. However, sex differences in BBB disruption beyond this 6h time point after TBI has not been studied. Therefore, our second objective was to assess potential sex-dependent differences in BBB disruption and subsequent NP accumulation following TBI. Ultimately, we revealed key sex-dependent considerations for NP delivery strategies following TBI.