The blood–brain barrier (BBB), as a fundamental dynamic metabolic interface that bi–directionally regulates fluid, solute and cellular transport barriers (Keaney and Campbell, 2015), prevents almost 100 % of large–molecule drugs and 98 % of small–molecule drugs from entering the brain, which poses a significant challenge to brain–targeted drug delivery. Therefore, it is critical to develop effective therapeutic drugs for PTSD.(See Fig. Traditional pharmacological treatments, mainly the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine, have low efficacy and significant side effects, such as mental retardation, and hypersensitivity (Friedman et al., 2011, Weathers and Keane, 2007). Post–traumatic stress disorder (PTSD) is a debilitating anxiety mental disorder caused by threats or traumatic events, resulting in abnormal physiological and psychological symptoms such as sleep disturbances and depression (Compean and Hamner, 2019, Herringa, 2017, Nohales and Prieto, 2018). In conclusion, this cell membrane bionic delivery system assisted with ultrasound had good therapeutic effect against PTSD mice, which is expected to help convey CBD to inflammatory areas within the brain and alleviate the symptoms of PTSD.

In our study, the potential of ultrasound to open BBBs and improve the brain–targeted delivery of CBD was evaluated. Brain targeting and excellent anti–PTSD effects of CMNVs had been validated in vivo by imaging and pharmacodynamics studies. In vitro anti–inflammatory, cellular uptake and pharmacokinetic experiments respectively verified the anti–inflammatory, inflammatory targeting and immune escape properties of CMNVs. Here, a bionic delivery system, camouflage CBD–loaded macrophage–membrane nanovesicles (CMNVs), was constructed via co–extrusion of CBD with macrophage membranes, which had inflammatory and immune escape properties. Our previous studies proved the effectiveness of cannabidiol (CBD) against PTSD, but low water solubility, low brain targeting efficiency and poor bioavailability restricted its applications.

However, the blood–brain barrier (BBB) prevents conventional drugs for PTSD from entering the brain. Post–traumatic stress disorder (PTSD), which normally follows psychological trauma, has been increasingly studied as a brain disease.

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