Angiopep-2 modified dual drug-loaded liposomes with brain targeting functionality mitigate Alzheimer’s disease-related symptoms in APP/PS-1 mice

The blood–brain barrier (BBB) is a barrier that maintains brain homeostasis, but it is also one of the major problems that must be overcome in the development of Alzheimer’s disease (AD) drugs. To solve this problem, Salidroside (Sal) and Icariin (Ica), drugs with neuroprotective effects were loaded into liposomes, and the targeting molecule Angiopep-2 was modified on the surface of liposomes (Ang-Sal/Ica-Lip), so that the constructed nano-drug delivery system could effectively cross the BBB and exert anti-AD effects. The prepared liposomes exhibited ideal physicochemical properties. In vitro and in vivo targeting studies showed that Ang-Sal/Ica liposome could cross the BBB to increase drug accumulation in the brain, and increase the uptake of N2a cells and bEnd.3 cells. The pharmacodynamic analysis in vivo showed that Ang-Sal/Ica liposome could reverse neuronal and synaptic damage, inhibit neuroinflammation and oxidative stress and improve learning and cognitive function. Therefore, Ang-Sal/Ica liposome may be a promising therapeutic strategy for mitigating AD-related symptoms.