School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China; Pharmaceutical College, Henan University, Kaifeng 475004, China.
Int J Pharm. 2023 Apr 25;637:122872. doi: 10.1016/j.ijpharm.2023.122872. Epub 2023 Mar 21.
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.
创伤后应激障碍（PTSD）通常是在心理创伤后发生的，它已越来越多地被研究为一种脑部疾病。然而，血脑屏障（BBB）会阻止用于 PTSD 的常规药物进入大脑。我们之前的研究证明了大麻二酚（CBD）对 PTSD 的有效性，但低水溶性、低脑靶向效率和差的生物利用度限制了其应用。在这里，通过将 CBD 与巨噬细胞膜共挤出，构建了一种仿生递药系统，伪装 CBD 负载的巨噬细胞膜纳米囊泡（CMNVs），它具有炎症和免疫逃逸特性。体外抗炎、细胞摄取和药代动力学实验分别验证了 CMNVs 的抗炎、炎症靶向和免疫逃逸特性。通过成像和药效学研究，在体内验证了 CMNVs 的脑靶向和优异的抗 PTSD 效果。在我们的研究中，评估了超声打开血脑屏障和提高 CBD 脑靶向递送的潜力。总之，这种细胞膜仿生递药系统联合超声具有很好的抗 PTSD 作用，有望帮助将 CBD 递送到大脑内的炎症区域，缓解 PTSD 症状。
