PEGylated Flavonoid Aspasomes as a Brain-Targeted Nano-Vesicular Platform for Enhanced Neuroprotection in Stress-Induced Cognitive Dysfunction

The study investigates PEGylated flavonoid Aspasomes as a brain-targeted nano-vesicular platform for neuroprotection in stress-induced cognitive dysfunction. The optimized formulation (F14) demonstrated high entrapment efficiency, nanosized vesicles, and enhanced drug release and nasal permeation compared to free luteolin (LUT). In chronic unpredictable stress rats, F14 significantly improved spatial memory and reduced depressive-like behavior more effectively than free LUT. Biochemical analysis showed superior reductions in hippocampal acetylcholinesterase activity and serum corticosterone, along with increased brain-derived neurotrophic factor levels. Histopathological examination confirmed preserved hippocampal architecture in treated rats. These findings suggest that PEGylated LUT-Aspasomes enhance stability, brain delivery, and neuroprotective efficacy, offering a promising approach for managing stress-related neurobehavioral disorders.