Cannabidiol-loaded biomimetic macrophage membrane vesicles against post-traumatic stress disorder assisted by ultrasound

Post-traumatic stress disorder (PTSD), which normally follows psychological trauma, has been increasingly studied as a brain disease. However, the blood-brain barrier (BBB) prevents conventional drugs for PTSD from entering the brain. 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. 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. In vitro anti-inflammatory, cellular uptake and pharmacokinetic experiments respectively verified the anti-inflammatory, inflammatory targeting and immune escape properties of CMNVs. Brain targeting and excellent anti-PTSD effects of CMNVs had been validated in vivo by imaging and pharmacodynamics studies. In our study, the potential of ultrasound to open BBBs and improve the brain-targeted delivery of CBD was evaluated. 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.