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

Yuanyuan Zhang,Yiguang Jin,Lina Du,Delian Wan,Qian Li,Qi Li,Jinglu Hu,Chunqing Wang,Qingwei Jiang

doi:10.3390/gels8020108

Abstract

(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.

Highlights

Microwave radiation, which refers to electromagnetic waves with a frequency of 300 MHz to 300 GHz, has various effects on many organs of the body, and the brain is generally considered to be the most susceptible organ for microwave radiation [1]
After the organs were removed, we found that the fluorescence of the p.o. group was mainly concentrated in the stomach while the fluorescence of the i.n group was distributed in the brain and other organs (Figure 4d), which proved that intranasal administration could achieve brain targeting
The inclusion complexes formed by cinnarizine and SBE-β-CD significantly improved the solubility of the drug

Summary

Introduction

Microwave radiation, which refers to electromagnetic waves with a frequency of 300 MHz to 300 GHz, has various effects on many organs of the body, and the brain is generally considered to be the most susceptible organ for microwave radiation [1]. Calcium channel blockers may become effective drugs for MIBI, with these including selective Ca2+ channel blockers, such as nifedipine, nimodipine, and diltiazem, and non-selective Ca2+ channel blockers, such as cinnarizine and flunarizine These blockers are characterized by the ability to inhibit the influx of extracellular calcium ions by blocking the calcium ion channels on cell membranes so that the vascular smooth muscles can be relaxed, the peripheral vascular resistance reduced, and the pharmacological effect of lowering blood pressure achieved. These drugs are used for the treatment of high blood pressure clinically but they are used for the treatment of coronary heart disease and angina pectoris [15]. There is the possibility that Ca2+ channel blockers can be used as promising therapeutic drugs against MIBI

Methods

Results

Conclusion