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.

To explore the effects of inhaling and smelling linalool acetate (LA) and 1, 8 eucalyptol (EO) on post-traumatic stress disorder (PTSD) like symptoms in mice.

Male C57BL/6J mice were randomly divided into the control group, model group, sertraline hydrochloride (Ser) positive control group, LA group, EO group, and LA+EO group (n=8). A PTSD mouse model was established using a brief electric shock method. The inhalation doses for LA and EO were detected by portable VOC analyzer respectively, while the oral dose for Ser was 10 mg/kg. On days 13, 16, and 18 after modeling, the anxiety-like and depression-like behaviors were assessed using the open field test, elevated plus maze, and forced swim test, respectively. Hematoxylin-eosin (HE) staining, biochemical colorimetric assays, and enzyme-linked immunosorbent assays (ELISA) were adopted to detect changes in the structure of hippocampal tissues, inflammatory factors of brain tissues, and oxidative stress levels, respectively.

Compared with the model group, the durations of freezing and immobility in LA, EO, and LA+EO groups were significantly reduced, along with a marked increase in total travel distance in the open field test. The percentage of time spent in the open arms of the elevated plus maze was also significantly elevated. Histological examination revealed an increase in the number of neuronal layers, with more organized arrangement and clearer cellular contours. Furthermore, significant reductions in neuroinflammation and effective alleviation of oxidative stress were observed in brain tissues. Among all the intervention groups, the EO group was the most pronounced in terms of improvement.

Both individual and alternating inhalation of LA and EO can significantly ameliorate PTSD-like symptoms in mice. Specifically, anxiolytic and antidepressant effects in the EO group are stronger than in the other two intervention groups, but the alternating inhalation of EO and LA produces no synergistic effect.