阿尔茨海默病（AD）是老年人常见的中枢神经系统退行性疾病，已成为继心脑血管疾病和肿瘤之后的第三大健康杀手。基于阿尔茨海默病是一种多病因、病理复杂的疾病，单一靶点的疗效必然有限，多环节、多靶点的协同作用有望取得更好的疗效。本研究的目的是基于课题组研发的治疗阿尔茨海默病的新型纳米药物递送系统，探讨壳聚糖修饰药物的脑靶向性。壳聚糖具有良好的生物相容性、生物吸附性，降解产物可起到保护和促进作用。选择神经细胞的再生与天然代表性胆碱酯酶抑制剂加兰他敏结合，开发出一种新型纳米给药系统，用于经鼻递送抗阿尔茨海默病，具有多靶点协同作用。对原药溶液和系统溶液静脉和鼻腔给药后的血液和脑组织药物浓度进行同步分析。脑靶向指数（DTI）用于评价纳米给药系统鼻内给药后的脑靶向效果。加兰他敏原药溶液和加兰他敏系统溶液静脉注射和鼻腔注射后的血药浓度表明，两种给药方式中静脉注射和鼻腔给药，相同给药方法下，系统达到最高血药浓度的时间点远高于原药。血浆样本和组织样本中加兰他敏的含量表明，加兰他敏系统静脉给药和鼻内给药后，同一时间点，脑组织中的药物浓度远大于加兰他敏原药，且持续时间长。也更长。脑组织中药物浓度依次为嗅球、嗅道、脑、小脑逐渐降低。在嗅球、嗅道、大脑、小脑等脑组织中，静脉注射加兰他敏系统的药物浓度低于鼻腔给药后的药物浓度。本研究得出结论，与原药液相比，纳米给药系统鼻腔给药有显着的脑靶向性，静脉注射也有脑靶向性。在嗅球、嗅道、大脑、小脑中，嗅球处的大脑靶向指数最高，靶向性最好。

Alzheimer's disease (AD), a common degenerative disease of the central nervous system in the elderly, has become the third largest health killer after cardiovascular and cerebrovascular diseases and tumors. Based on the fact that Alzheimer's disease is a disease with multiple etiologies and complex pathology, a single target is bound to have a limited curative effect, and the synergy of multiple links and multiple targets is expected to achieve a better curative effect. The aim of this study is to investigate the brain targeting of a drug modified by chitosan, based on the new nanodrug delivery system for treating Alzheimer's disease developed by the research group.Chitosan with good biocompatibility, biosorption, and degradation products that can protect and promote the regeneration of nerve cells was selected to combine with galantamine, a natural representative cholinesterase inhibitor, to develop a new nano drug delivery system for nasal delivery of anti-Alzheimer's disease with a multi-target synergistic effect. Synchronous analysis was conducted on the blood and brain tissue drug concentrations after intravenous and nasal administration of the original drug solution and system solution. The brain targeting index (DTI) is used to evaluate the brain targeting effect of the nano-drug delivery system after intranasal administration.The blood concentration of galantamine original drug solution and galantamine system solution after intravenous injection and nasal show that in the two administration methods of intravenous injection and nasal administration, under the same administration method, the time point of the system reaching the highest blood drug concentration is much higher than that of the original drug. The content of galantamine in plasma samples and tissue samples indicate that after intravenous administration and intranasal administration of the galantamine system, at the same time point, the drug concentration in brain tissue was far greater than that of the original drug of galantamine, and the duration was also longer. The concentration of drugs in brain tissue decreased gradually in the order of olfactory bulb, olfactory tract, brain, and cerebellum. In the brain tissues of the olfactory bulb, olfactory tract, cerebrum, and cerebellum, the drug concentration of the galantamine system after intravenous injection is lower than that after nasal administration.This study concludes that compared with the original drug solution, the nano drug delivery system has significant brain targeting for nasal administration, and intravenous injection also has brain targeting. In the olfactory bulb, olfactory tract, brain, and cerebellum, the brain targeting index at the olfactory bulb is the highest, and the targeting is the best.