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 disruption1,2. 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 TBI3,4. 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 injury5,6. 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.