Nasal Delivery of Cinnarizine Thermo- and Ion-Sensitive In Situ Hydrogels for Treatment of Microwave-Induced Brain Injury.

(1) Background: When the body is exposed to microwave radiation, the brain is more susceptible to damage than other organs. However, few effective drugs are available for the treatment of microwave-induced brain injury (MIBI) because most drugs are difficult to cross the blood-brain barrier (BBB) to reach the brain. (2) Methods: Nasal cinnarizine inclusion complexes with thermo-and ion-sensitive hydrogels (cinnarizine ISGs) were prepared to treat MIBI and the characteristics of the inclusion complexes and their thermo-and ion-sensitive hydrogels were evaluated. (3) Results: Due to high viscosity, cinnarizine ISGs can achieve long-term retention in the nasal cavity to achieve a sustained release effect. Compared with the model, the intranasal thermo-and ion-sensitive cinnarizine ISGs significantly improved the microwave-induced spatial memory and spontaneous exploration behavior with Morris water maze and open field tests. Cinnarizine ISGs inhibited the expression of calcineurin and calpain 1 in the brain, which may be related to the inhibition of calcium overload by cinnarizine. (4) Conclusion: Intranasal thermo- and ion-sensitive cinnarizine ISGs are a promising brain-targeted pharmaceutical preparation against MIBI.