Intranasal delivery of macrophage cell membrane cloaked biomimetic drug-nanoparticle system attenuates acute lung injury

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Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), a life-threatening disease, is typically induced by uncontrolled inflammatory responses and excessive production of reactive oxygen species (ROS). Astaxanthin (Ast) is known for its powerful natural antioxidant properties, showcasing excellent antioxidant, anti-inflammatory, and immunomodulatory effects. However, its poor water solubility and bioavailability significantly limit its efficacy. Taking inspiration from biomimetic biology, this study developed a nasal drug delivery system comprising macrophage membrane (Mϕ)-encapsulated Ast-loaded nanoparticles (Mϕ@Ast-NPs) for the treatment of ALI. Mϕ@Ast-NPs retain the original homing properties of Mϕ, enabling targeted delivery to inflamed lungs and enhancing the anti-inflammatory effects of Astaxanthin (Ast). In vitro and in vivo, Mϕ@Ast-NPs demonstrated excellent biocompatibility and safety, as evidenced by no hemolysis of red blood cells and no significant toxic effects on cells and major organs. To determine the inflammation-targeting of Mϕ@Ast-NPs, both healthy and ALI mice were intranasally administered with Mϕ@Ast-NPs, the results demonstrated that highly targeting to inflamed lungs and endothelia, while with minimal accumulation in healthy lungs and endothelia. Mϕ@Ast-NPs effectively inhibited ROS production, enhanced Nrf2 expression and nucleus translocation, and reduced the levels of pro-inflammatory factors such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) in LPS-induced RAW264.7 cells and ALI mice. Our study provided a safe and effective nasal delivery platform for pulmonary diseases, and this biomimetic nano-formulation of Ast could be as functional foods in the future.