Mesenchymal stem cell membrane functionalized vesicles for Baicalein targeted delivery in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory impairment. The lack of effective therapeutic strategies underscores the urgent need for disease-modifying therapies. Baicalein (Bai), a natural compound, exhibits multi-target properties and diverse pharmacological activities, positioning it as a promising candidate. However, its therapeutic potential in AD is limited by low bioavailability and inadequate brain accumulation. To overcome these challenges, we developed mesenchymal stem cell membrane-functionalized vesicles for targeted Bai delivery (MSC-Bai-Lipo). Using Box-Behnken response surface methodology, we optimized preparation parameters to achieve high encapsulation efficiency. In AD model mice, MSC-Bai-Lipo demonstrated targeted delivery to lesions, exhibiting superior therapeutic effects by mitigating AD-associated neuronal damage and neuroinflammatory processes.