Rungta College of Pharmaceutical Sciences and Research, Kohka-Kurud Road, Bhilai, Chhattisgarh 490024, India.
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh 492010, India.
J Control Release. 2018 Jul 10;281:139-177. doi: 10.1016/j.jconrel.2018.05.011. Epub 2018 May 24.
According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD. The therapeutic efficacy of the drug is not only affected by its reduced concentration in the brain owing to the existence of blood-brain-barrier (BBB) but also due to its low brain permeability. In this context, the intranasal (IN) route of drug administration has emerged as an alternative route over the systemic (oral and parenteral) drug delivery to the brain. The delivery of the drug via an IN route offers various advantages over systemic drug delivery system, as it directly delivers the drug into the brain via olfactory route. Presence of drug in the olfactory bulb, in turn, increases the drug bioavailability in the brain and reduces the drug degradation as well as wastage of the drug through` systemic clearance. However, there is also some limitation associated with IN like poor drug permeation through the nasal mucosa and mucociliary clearance. The delivery system various through novel strategies (nano drug carrier system, colloidal carriers, mucoadhesive devices, controlled delivery system, pro-drug, etc.) are adapted to overcome the above-stated limitations. Although, after all, such successful research claims, very few of the nose-to-brain drug delivery of anti-AD drugs have gained market approval due to lack of sufficient clinical evidence. Onzetra Xsail® is one such marketed preparations approved for IN delivery used for the treatment of a brain disorder; migraine. In the field of patents also, no work is found which could present sufficient experimental findings to support its clinical safety profile. It also underlines the fact that majority of work related to the nose-to-brain delivery of anti-AD drugs is limited only up to preclinical studies. In this review article, we have discussed the latest works on various novel formulations loaded with various anti-Alzheimer agents. These agents include galantamine, deferoxamine, tacrine, tarenflurbil, rivastigmine, risperidone, curcumin, quercetin, piperine, insulin, etc. and various peptides towards the development of a promising IN drug delivery system for the treatment of AD. Through this review article, we want to drag the attention of the researchers working in this field towards the challenges and hurdles of practical applicability IN delivery of anti-AD drugs. Moreover, the attention towards the clinical studies will ease the approval process for the administration of anti-Alzheimer drugs via IN route.
根据阿尔茨海默病协会报告(2017 年),阿尔茨海默病(AD)是美国第六大主要死亡原因,影响近 550 万人。仅在 2017 年,美国 AD 治疗费用就已报告上升至 2590 亿美元。这一统计数据显示了该疾病在美国的严重程度,在全球范围内非常相似。另一方面,治疗方法仍然仅限于少数几种经美国食品和药物管理局(FDA)批准的常规口服药物。这些药物主要从轻度到中度 AD 发挥作用。药物的治疗效果不仅受到血脑屏障(BBB)存在导致的其在大脑中的浓度降低的影响,还受到其脑通透性低的影响。在这种情况下,与全身(口服和肠胃外)药物输送相比,鼻内(IN)药物给药途径已成为向大脑输送药物的替代途径。通过 IN 途径给药提供了优于全身药物输送系统的各种优势,因为它通过嗅觉途径直接将药物输送到大脑。药物存在于嗅球中,反过来又增加了药物在大脑中的生物利用度,并减少了药物通过全身清除而降解和浪费。然而,IN 也存在一些限制,例如药物通过鼻腔黏膜的渗透性差和粘液清除率高。通过各种新策略(纳米药物载体系统、胶体载体、粘膜粘附装置、控释系统、前药等)来适应输送系统,以克服上述限制。尽管如此,由于缺乏足够的临床证据,很少有抗 AD 药物的鼻内脑输送获得市场批准。Onzetra Xsail®是一种已上市的批准用于 IN 输送的制剂,用于治疗脑部疾病;偏头痛。在专利领域,也没有发现任何工作能够提供足够的实验结果来支持其临床安全性概况。这也强调了一个事实,即大多数与抗 AD 药物的鼻内脑输送相关的工作仅局限于临床前研究。在这篇综述文章中,我们讨论了各种新型制剂中负载各种抗阿尔茨海默氏症药物的最新工作。这些药物包括加兰他敏、去铁胺、他克林、他仑氟韦、利斯的明、利培酮、姜黄素、槲皮素、胡椒碱、胰岛素等,以及各种肽,以开发一种有前途的 IN 药物输送系统,用于治疗 AD。通过这篇综述文章,我们希望引起该领域研究人员对 IN 输送抗 AD 药物实际适用性的挑战和障碍的关注。此外,对临床研究的关注将简化通过 IN 途径管理抗阿尔茨海默氏症药物的审批程序。
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