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There are currently no alternatives that mimic the nose-to-brain pathway, which is very complex. The experiments in vitro could not fully disclose the delivery efficiency and safety assessment of the formulation in vivo. A total of 120 male Sprague Dawley (SD) rats (12 weeks old) with body weights between 300 to 320 g were housed at a temperature of 22 \u00b1 2\u2103, a relative humidity of 50 \u00b1 2%, and a 12-h dark light cycle. All the experimental rats took food and drank water as they pleased. In order to minimize rats suffering, the invasive surgeries on rats were performed under anesthesia (intraperitoneal injections with 3% sodium pentobarbital (1.5 mL\/kg)). In addition, invasive operations were performed by skilled technicians in order to speed up operations and reduce the size of the surgical area for rats, which maximized the survival rate of rats and reduced the number of rats in the experiments. At the end of the study, the rats were anesthetized by intraperitoneal injection of sodium pentobarbital and then euthanized in a thermostatically controlled dark box filled with 70% CO<sub>2<\/sub>. The study has adhered to the ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval and Informed Consent"}}]}}