To design and synthesize a mannose-modified PLGA-PEG nanodrug delivery system capable of brain-targeting accumulation and blood-brain barrier (BBB) permeation.

bEnd.3 mouse vascular endothelial cells were used to establish a monolayer cell model using Transwell chambers. The barrier integrity was evaluated by measuring the transendothelial electrical resistance before an in vitro BBB model was established. A post-traumatic stress disorder model was established to find out about the in vivo BBB permeability of nanomaterials. In the in vitro experiment, nanomaterials were delivered to BV2 cells while in the in vivo experiment, nanomaterials were injected into the tail vein of C57BL/6 mice. The ability of nanomaterials to penetrate the blood-brain barrier was detected by a spectrophotometer, laser confocal microscopy and flow cytometry. The distribution and rate of brain enrichment of nanomaterials were dynamically monitored by a small animal in vivo near-infrared fluorescence imaging system.

In vitro experiments showed that the PPM system loaded with a fluorescent molecule, purpurin 18 (P18), could effectively penetrate the BBB with a fluorescence permeability of 7%. The system was capable of both prolonged retention in the brain with a brain accumulation rate of 30%, and significant brain enrichment in a post-traumatic stress disorder (PTSD) mouse model with an enrichment efficiency of 54%.

The newly developed BBB-penetrating nano-delivery system can ensure effective BBB penetration and targeted delivery in PTSD mouse models, with significant implications and translational potential for neuropharmaceutical development.