An efficient brain delivery system co-loaded with multiple components of for synergistic treatment of ischemic stroke.

Ischemic stroke is a neurological disease characterized by high morbidity and mortality. A key pathological mechanism involves rapid restoration of blood oxygen in the infarcted area, which triggers oxidative stress and inflammatory responses leading to neuronal damage. The complex etiology of the disease poses challenges to single-target pharmacotherapy, necessitating the development of multi-targeted combination drug treatments. Reports showed that water- and lipid-soluble components of Danshen, exert synergistic neuroprotective effects. However, the disparate physicochemical properties of these compounds lead to differential release kinetics, hampering the therapeutic efficacy. Furthermore, the blood-brain barrier (BBB) presents a formidable obstacle to the penetration of water-soluble constituents. Here, we developed a novel biomimetic drug delivery system utilizing hollow polydopamine coated with red blood cell membranes. Water-soluble (W) and lipid-soluble (L) components of Danshen were loaded at distinct membrane regions to facilitate synchronized release profile. Additionally, borneol was used to modify the membrane to enhance the BBB penetration capacity. Mechanism study revealed that W and L possess synergistic effect through inhibiting NF-κB and TNF-α pathways. In summary, this delivery system enables concurrent loading and efficient brain delivery of multiple constituents, thereby promoting neurological recovery and presenting a promising therapeutic strategy for ischemic stroke.