ApoE-modified liposomes encapsulating resveratrol and salidroside alleviate manifestations of Alzheimer’s disease in APP/PS-1 mice

Abstract

Objective

Alzheimer’s disease (AD) is a neurodegenerative disease that is associated with aging and is influenced by both genetic and environmental factors. Several studies and clinical trials have demonstrated that resveratrol (Res) and salidroside (Sal) are not only biologically safe but also influence AD biomarker trajectories. However, their clinical applications have been quite limited due to poor specificity, low solubility, and insufficient blood–brain barrier (BBB) penetration. Therefore, we developed a nano-drug delivery system in which Res and Sal were encapsulated in liposomes, which were surface-modified with ApoE (ApoE-Res/Sal-Lips) to compensate for these deficiencies.

Method

In this study, ApoE-Res/Sal-Lips were prepared using a standard thin-film hydration method for liposomes. Then, cellular uptake of the loaded liposomes was assessed in vitro using fluorescent staining assays. A BBB model was constructed to investigate the capacity of the liposomes to cross the BBB in vitro, and the ability of liposomes to target the brain was observed by in vivo imaging. In addition, the neuroprotective effects of the different liposome formulations in APP/PS-1 mice were evaluated by measuring the changes in levels of oxidative, anti-inflammatory, and anti-apoptotic factors in the mice brains.

Results

In vitro, ApoE-Res/Sal-Lips increased the uptake of Res and Sal by bEnd.3 and N2a cells, enhanced BBB penetration, and improved transport efficiency. In vivo, the ApoE-Res/Sal-Lips were found to alleviate AD pathological symptoms, reduce learning and memory impairments, and improve brain function.

Conclusion

ApoE-Res/Sal-Lips provide a new method for the treatment of AD.

Keywords:

• ApoE
• resveratrol
• salidroside
• liposomes
• blood-brain barrier
• Alzheimer’s disease

Ethics approval

All researches and animal care are strictly carried out in accordance with the Provision and General Recommendation of Chinese Experimental Animals Administration Legislation and all experiments were approved by the ethics committee of Liaoning University of traditional Chinese medicine.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

China Postdoctoral Science Foundation (2022MD723796), the Doctoral Startup Foundation of Liaoning Province (2023-BS-139).