UCIBIO/REQUIMTE, MEDTECH Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, 4050-313, Portugal.
Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King's College London, London, SE1 9NH, UK.
Int J Nanomedicine. 2021 Jun 29;16:4373-4390. doi: 10.2147/IJN.S305851. eCollection 2021.
Current treatments for Alzheimer's disease (AD) attenuate the progression of symptoms and aim to improve the patient's quality of life. Licensed medicines are mostly for oral administration and are limited by the difficulty in crossing the blood-brain barrier (BBB). Here in, the nasal route has been explored as an alternative pathway that allows drugs to be directly delivered to the brain via the nasal cavity. However, clearance mechanisms in the nasal cavity impair the delivery of drugs to the brain and limit their bioavailability. To optimize nose-to-brain delivery, formulations of lipid-based nanosystems, namely nanoemulsions and nanostructured lipid carriers (NLC), formulated in situ gelling hydrogels have been proposed as approaches for nose-to-brain delivery. These formulations possess characteristics that facilitate drug transport directly to the brain, minimizing side effects and maximizing therapeutic benefits. It has been recommended that the manufacture of these drug delivery systems follows the quality by design (QbD) approach based on nasal administration requirements. This review provides an insight into the current knowledge of the AD, highlighting the need for an effective drug delivery to the brain. Considering the mounting interest in the use of nanoemulsions and NLC for nose-to-brain delivery, a description of drug transport pathways in the nasal cavity and the application of these nanosystems and their in situ hydrogels through the intranasal route are presented. Relevant preclinical studies are summarised, and the future prospects for the use of lipid-based nanosystems in the treatment of AD are emphasized.
目前用于治疗阿尔茨海默病（AD）的方法可以减轻症状的进展，并旨在提高患者的生活质量。已批准的药物主要为口服制剂，其受到血脑屏障（BBB）通透性差的限制。在此，人们探索了鼻腔给药途径作为一种替代途径，使药物可以通过鼻腔直接递送至大脑。然而，鼻腔中的清除机制会削弱药物向大脑的传递，并限制其生物利用度。为了优化脑内递药，已提出原位形成凝胶的脂质纳米系统（即纳米乳剂和纳米结构脂质载体（NLC））制剂作为脑内递药的方法。这些制剂具有促进药物直接向大脑转运的特性，可以最小化副作用并最大化治疗效果。建议根据鼻腔给药要求，采用基于质量源于设计（QbD）的方法来制造这些药物递送系统。本文综述了 AD 的最新知识，强调了将有效药物递送至大脑的必要性。考虑到人们对纳米乳剂和 NLC 经鼻腔递药的兴趣日益浓厚，本文介绍了药物在鼻腔中的转运途径，以及这些纳米系统及其原位凝胶通过鼻内途径的应用。总结了相关的临床前研究，并强调了脂质纳米系统在 AD 治疗中的未来应用前景。
