经鼻腔给药至脑:关键靶点探索及主要考虑因素
Drug delivery to the brain via the nasal route of administration: exploration of key targets and major consideration factors.
作者信息
Jeong Seung-Hyun, Jang Ji-Hun, Lee Yong-Bok
机构信息
College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju, 61186 Republic of Korea.
Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14214 USA.
出版信息
J Pharm Investig. 2023;53(1):119-152. doi: 10.1007/s40005-022-00589-5. Epub 2022 Jul 24.
BACKGROUND
Cranial nerve-related diseases such as brain tumors, Alzheimer's disease, and epilepsy are serious diseases that continue to threaten human. Brain-related diseases are increasing worldwide, including in the United States and Korea, and these increases are closely related to the exposure to harmful substances and excessive stress caused by rapid industrialization and environmental pollution. Drug delivery to the brain is very important for the effective prevention and treatment of brain-related diseases. However, due to the presence of the blood-brain barrier and the extensive first-pass metabolism effect, the general routes of administration such as oral and intravenous routes have limitations in drug delivery to the brain. Therefore, as an alternative, the nasal-brain drug delivery route is attracting attention as a route for effective drug delivery to the brain.
AREAS COVERED
This review includes physiological factors, advantages, limitations, current application status, especially in clinical applications, and the necessary factors for consideration in formulation development related to nasal-brain drug delivery.
EXPERT OPINION
The nasal-brain drug delivery route has the advantage of enhancing drug delivery to the brain locally, mainly through the olfactory route rather than the systemic circulation. The nasal-brain lymphatic system has recently attracted attention, and it has been implied that the delivery of anticancer drugs to the brain nervous system is possible effectively. However, there are limitations such as low drug permeability, as well as nasal mucosa and the mucociliary system, as obstacles in nasal-brain drug delivery. Therefore, to overcome the limitations of nasal-brain drug delivery, the use of nanocarriers and mucoadhesive agents is being attempted. However, very few drugs have been officially approved for clinical application via the nasal-brain drug delivery route. This is probably because the understanding of and related studies on nasal-brain drug delivery are limited. In this review, we tried to explore the major considerations and target factors in drug delivery through the nasal-brain route based on physiological knowledge and formulation research information. This will help to provide a mechanistic understanding of drug delivery through the nasal-brain route and bring us one step closer to developing effective formulations and drugs in consideration of the key factors for nasal-brain drug delivery.
背景
诸如脑肿瘤、阿尔茨海默病和癫痫等与颅神经相关的疾病是持续威胁人类的严重疾病。包括美国和韩国在内,全球范围内与脑相关的疾病正在增加,这些增加与快速工业化和环境污染导致的有害物质暴露及过度压力密切相关。药物向脑内递送对于有效预防和治疗与脑相关的疾病非常重要。然而,由于血脑屏障的存在以及广泛的首过代谢效应,口服和静脉注射等常规给药途径在药物向脑内递送方面存在局限性。因此,作为一种替代方法,鼻脑给药途径作为向脑内有效递送药物的途径正受到关注。
涵盖领域
本综述包括生理因素、优点、局限性、当前应用状况,特别是在临床应用方面,以及与鼻脑给药相关的制剂开发中需考虑的必要因素。
专家意见
鼻脑给药途径具有局部增强药物向脑内递送的优势,主要通过嗅觉途径而非体循环。鼻脑淋巴系统最近受到关注,并且有人暗示有效地将抗癌药物递送至脑神经系统是可能的。然而,鼻脑给药存在诸如药物渗透性低以及鼻黏膜和黏液纤毛系统等障碍的局限性。因此,为克服鼻脑给药的局限性,正在尝试使用纳米载体和黏膜黏附剂。然而,极少有药物通过鼻脑给药途径获得正式批准用于临床应用。这可能是因为对鼻脑给药的理解和相关研究有限。在本综述中,我们试图基于生理学知识和制剂研究信息探索通过鼻脑途径给药的主要考虑因素和目标因素。这将有助于提供对通过鼻脑途径给药的机制理解,并使我们在考虑鼻脑给药的关键因素的基础上更接近开发有效的制剂和药物。