Introduction
Stroke remains the second leading cause of death and the third leading cause of death and disability combined in the world, as reported in 2019 Global Burden of Disease Study. Ischemic stroke is caused by a narrowing or blockage of the blood vessels supplying the brain, resulting in brain tissue dysfunction and necrosis, with high incidence, mortality, and disability rate. Of note, intranasal administration with MM-Lip-Rg3/PNS, a biomimetic nanoformulation coated with macrophage membrane and loaded with ginsenoside Rg3 (Rg3) as well as Panax notoginseng saponins (PNS) liposomes, may be a novel effective way to treat ischemic stroke.
About stroke
Stroke, also known as cerebrovascular accident or brain attack, is caused by obstruction or rupture of brain blood vessels, including ischemic stroke and hemorrhagic stroke. According to the Huangdi Neijing, a classic book of traditional Chinese medicine, stoke is caused by exogenous wind evil. It has typical syndromes of weakness or numbness of the face, hand and foot, visual disturbances, difficulty speaking or very severe headaches, which may eventually lead to hemiplegia, disability or even death. The five major risks for stroke globally include high systolic blood pressure, high body mass index, high fasting glucose, environmental particulate matter pollution, and smoking.
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Uniqueness of MM-Lip-Rg3/PNS
MM-Lip-Rg3/PNS exhibits favorable physical and chemical properties, including high encapsulation efficiency, small particle size, and excellent stability. On the one hand, bilayer structure of liposomes allows the encapsulation of lipophilic drugs (Rg3) in hydrophobic lipid bilayers and hydrophilic drugs (PNS) in hydrophilic cores, showing high dispersibility and good uniformity. On the other hand, MM-Lip-Rg3/PNS inherits the biological characteristics of macrophages, avoiding macrophage phagocytosis. It actively responds to and binds with inflammatory brain endothelial cells, enhancing its ability to traverse the blood brain barrier.
Efficacy of intranasal administration with MM-Lip-Rg3/PNS on ischemic stroke
Unlike oral administration, intranasal administration can bypass the first pass effect of the liver, thereby increasing drug delivery efficiency into the brain. Compared to intravenous administration, intranasal administration is non-invasive and can alleviate patient pain, with safety and convenience.
MM-Lip-Rg3/PNS can specifically target ischemic sites (DTI value > 1), even microglia, and increase the cumulative number of drugs in the ischemic hemisphere. This approach exhibits improved pharmacokinetic behavior, extends half-life, and increases drug bioavailability in the brain. Furthermore, it effectively alleviates brain inflammation (downregulation of TNF-α, IL-6, and IL-1β), reduces brain oedema, and diminishes infarct area (saline group: 35.3%; MM-Lip-Rg3/PNS group: 7.8%).
Conclusion
The designed biomimetic liposomes via intranasal administration exhibits good inflammatory reactivity and effectively protects brain tissues from damage, offering a promising new strategy for the treatment of stroke.
Reference
[1] GBD 2019 Stroke Collaborators. Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20(10):795-820. doi:10.1016/S1474-4422(21)00252-0
[2] Liu T, Zhang M, Zhang J, et al. Targeted Delivery of Macrophage Membrane Biomimetic Liposomes Through Intranasal Administration for Treatment of Ischemic Stroke. Int J Nanomedicine. 2024;19:6177-6199. doi:10.2147/IJN.S458656
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