Neuroprotective Effect of Ultrasound Triggered Astaxanthin Release Nanoparticles on Early Brain Injury After Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a fatal disease. Within 72 h of SAH, the intracranial blood-brain barrier (BBB) is destroyed, and the nerve cells have responses such as autophagy, apoptosis, and oxidative stress. Antioxidation is an essential treatment of SAH. Astaxanthin (ATX) induces cells’ antioxidant behaviors by regulating related signal pathways to reduce the damage of brain oxidative stress, inflammation, and apoptosis. Because of its easy degradability and low bioavailability, ATX is mainly encapsulated with stimulus-responsive nanocarriers to improve its stability, making it rapidly release in the brain and efficiently enter the lesion tissue. In this study, the ultrasonic cavitation agent perfluorocarbon (PFH), ATX, and fluorescent dye IR780 were loaded with polydopamine (PDA) to prepare a US triggered release nanoparticles (AUT NPs). The core-shell structure of AUT NPs formed a physical barrier to improve the bioavailability of ATX. AUT NPs have high ATX loading capacity and US responsiveness. The experimental results show that the AUT NPs have high stability in the physiological environment. Both US and pH stimuli can trigger the release. Under US, PFH breaks through the rigid shell. The structure of AUT NPs is destroyed in situ, releasing the loaded drugs into neuronal cells to realize the antioxidant and antiapoptotic effects. The in vivo experiment results show that the AUT NPs have good biosafety. They release the drugs in the brain under stimuli. The in vivo treatment results also show that AUT NPs have an excellent therapeutic effect. This approach presents an experimental basis for the establishment of Innovative SAH treatments.