G d'Annunzio University, School of Pharmacy, Department of Drug Sciences, Via dei Vestini 31, 66100 Chieti, Italy.
Expert Opin Drug Deliv. 2011 May;8(5):581-603. doi: 10.1517/17425247.2011.561311. Epub 2011 Mar 11.
Current Alzheimer's disease (AD) therapy is based on the administration of the drugs donepezil, galantamine, rivastigmine and memantine. Until disease-modifying therapies become available, further research is needed to develop new drug delivery strategies to ensure ease of administration and treatment persistence.
In addition to the conventional oral formulations, a variety of drug delivery strategies applied to the treatment of AD are reviewed in this paper, with a focus on strategies leading to simplified dosage regimens and to providing new pharmacological tools. Alternatives include extended release, orally disintegrating or sublingual formulations, intranasal or short- and long-acting intramuscular or transdermal forms, and nanotechnology-based delivery systems.
The advent of new research on molecular mechanisms of AD pathogenesis has outlined new strategies for therapeutic intervention; these include the stimulation of α-secretase cleavage, the inhibition of γ-secretase activity, the use of non-steroidal anti-inflammatory drugs, neuroprotection based on antioxidant therapy, the use of estrogens, NO synthetase inhibitors, and natural agents such as polyphenols. Unfortunately, these compounds might not help patients with end stage AD, but might hopefully slow or stop the disease process in its early stage. Nanotechnologies may prove to be a promising contribution in future AD drug delivery strategies, in particular drug carrier nano- or microsystems, which can limit the side effects of anti-Alzheimer drugs.
目前，阿尔茨海默病（AD）的治疗基于多奈哌齐、加兰他敏、利伐斯的明和美金刚这几种药物的应用。在出现疾病修饰疗法之前，还需要进一步研究以开发新的药物输送策略，以确保易于给药和治疗的持续性。
除了常规的口服制剂，本文还综述了应用于 AD 治疗的多种药物输送策略，重点关注可简化剂量方案并提供新的药理学工具的策略。这些替代方案包括延长释放、口服崩解或舌下制剂、鼻内或短效和长效肌内或透皮制剂，以及基于纳米技术的输送系统。
AD 发病机制的分子机制的新研究的出现，为治疗干预制定了新策略；这些策略包括刺激α-分泌酶裂解、抑制γ-分泌酶活性、使用非甾体抗炎药、基于抗氧化治疗的神经保护、使用雌激素、一氧化氮合酶抑制剂和多酚等天然药物。不幸的是，这些化合物可能无助于晚期 AD 患者，但有望在疾病早期阶段减缓或阻止疾病进程。纳米技术可能会成为未来 AD 药物输送策略的一个有前途的贡献，特别是药物载体纳米或微系统，可限制抗阿尔茨海默病药物的副作用。
