阿尔茨海默症(Alzheimer's Disease, AD)是一种非常常见的进行性和破坏性中枢神经系统的退行性疾病,对老年人的生活质量产生影响,对老年人的生命安全造成严重危害,给家庭、社会和国家带来了巨大的经济负担。目前治疗AD的药物尚未取得较大突破和创新,面临着突破血脑屏障的挑战,且治疗方法不当可能会导致患者产生不良反应。靶向载药系统作为一种有效的治疗方式,能够显著降低血液中的药物浓度、给药频率和药物毒副作用,同时提高药物在目标部位的浓度和疗效以及药物生物利用度,还能对药物起到缓释效果。此外,靶向载药系统还有望穿透血脑屏障,提高血脑渗透率,实现脑靶向性,精准递送药物,从而为治疗AD提供了一条高效且安全的途径。本工作综述了AD的发病机制、AD的治疗辅助药物、非药物治疗方法以及针对Aβ聚集、乙酰胆碱酶抑制和受体拮抗等主要药物的作用机理和副作用,并对磁性纳米颗粒、脂质体等针对治疗AD的靶向载药系统进行了简单的介绍、梳理及总结,指出了现在存在的问题,提出了可能的解决方案,指明了未来可能发展的方向。
Alzheimer's disease (AD) is a very common progressive and destructive degenerative disease of the central nervous system that affects the quality of life of the elderly and poses a serious risk to their lives, placing a huge economic burden on families, society and the state. There are not many breakthroughs as well as innovations in current medications for the treatment of AD, and there is also the challenge of breaking through the blood-brain barrier, and improper treatment may lead to adverse reactions in patients. Targeted drug delivery system, as an effective therapeutic modality, can significantly reduce the concentration of drugs in the blood, the frequency of drug delivery and the drug toxicity, while increasing the concentration and efficacy of drugs at the target site and drug bioavailability, as well as providing a slow-release effect for drugs. In addition, the targeted drug delivery system is also expected to penetrate the blood-brain barrier, improve blood-brain penetration, realize brain targeting, and deliver drugs precisely, thus providing an efficient and safe way to treat AD. This work reviews the pathogenesis of AD, the non-pharmacological methods of adjuvant drug therapy for the treatment of AD as well as the mechanism of action and side effects of the main drugs targeting amyloid β protein (Aβ) aggregation, acetylcholinesterase inhibition, and receptor antagonism, etc. It also briefly introduces and combs through as well as summarizes the targeting drug delivery systems for the treatment of AD such as magnetic nanoparticles, liposomes, and so forth, points out the problems that exist at the moment, puts forward the possible solutions, and indicates the direction of possible development in the future.