Effects of atorvastatin-loaded PEGylated liposomes delivered by magnetic stimulation for stroke treatment

Abstract

Background: Focused magnetic stimulation (MagStim) can temporarily and safely open the blood-brain barrier (BBB) for target delivery. We investigated whether opening the BBB with MagStim and delivering atorvastatin-loaded PEGylated liposomes (LipoStatin) would work synergistically for subacute post-stroke treatment. Methods: Two weeks after middle cerebral artery occlusion (MCAO), an injection of 15 mg/ml magnetic nanoparticles (MNPs) was performed, followed by 30 min of MagStim, in subacute stroke models. The procedure was conducted over a week, during which MagStim and MNPs were administered three times at two-day intervals, and LipoStatin (10 mg/kg) was injected immediately after each MagStim treatment. We investigated the motor function, BBB integrity, neuroinflammation, and neurogenesis three weeks after stroke (Sham vs. Control vs. LipoStatin vs. MagStim + LipoStatin). Results: The MagStim + LipoStatin group showed improved motor function compared to the Control (p = 0.007) group. The MagStim + LipoStatin group significantly reduced infarct volume and improved BBB integrity compared to the control and LipoStatin groups. In the MagStim + LipoStatin group, the expression of TNF-α was reduced (p = 0.020) compared to the LipoStatin group, and eNOS was enhanced (p = 0.037) compared to the Control group. Markers for neurogenesis were also considerably increased in the MagStim + LipoStatin group compared to the Control and LipoStatin groups (p < 0.0001). Conclusions: Our study demonstrates the beneficial synergistic effects of MagStim and the target delivery of LipoStatin in subacute ischemic stroke. These findings underscore the need for future advancements in promising novel non-invasive MagStim methods and nanotherapeutic hybrid approaches for target drug delivery and treatment in post-stroke recovery. © 2025 Elsevier B.V., All rights reserved.