Drug delivery to the brain via the nasal route of administration: exploration of key targets and major consideration factors

Abstract

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.

Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System

“…In this study on mice, we clearly demonstrate intranasal delivery of the GM 1 -liposomes into the mouse brain and GBM via the nasal-brain-lymphatic system, bypassing the BBB. Our data are consistent with the results of other studies suggesting that intranasal administration of therapeutics is an effective method for brain drug delivery [ 9 , 10 , 11 , 12 , 13 ]. In the experiments with ablation of the MLVs, we report an important role of the meningeal “door” for transport of liposomes from the nasal cavity to the brain tissues.…”

“…The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB [ 9 , 10 , 11 , 12 , 13 ]. Intranasal delivery is based on the direct anatomic route between the olfactory neuroepithelium and the brain.…”

“…Intranasal delivery is based on the direct anatomic route between the olfactory neuroepithelium and the brain. However, in most cases, after intranasal administration of drugs, their concentration in the brain is not sufficient to achieve a therapeutic effect [ 9 , 10 , 11 , 12 , 13 ]. Therefore, it is necessary to develop technologies to overcome the obstacles facing nose-to-brain delivery of promising pharmaceuticals.…”

Intranasal Polymeric and Lipid-Based Nanocarriers for CNS Drug Delivery

“…(2) In the respiratory region of the nasal cavity, drugs can be endocytosed by the trigeminal nerve and travel along the axon to reach the CNS or can cross epithelial cells to reach the blood. (3) Once in the blood, drugs administered intranasally must cross the BBB to reach the CNS [ 108 ] (Created in ; accessed on 2 February 2023).…”

Molecular Mind Games: The Medicinal Action of Cyclodextrins in Neurodegenerative Diseases

“…Intranasal administration has been recently proposed as a suitable delivery route to bypass the blood-brain barrier and target the central nervous system, having as an advantage the fact that it is quite less invasive than intrathecal administration. While its efficacy in the administration of small molecules such as sedatives, anxiolytics and corticosteroids is well demonstrated [ 71 ], the delivery of substances of high molecular weight can be trickier, prompting a case-by-case evaluation. A study comparing the distribution and tissue concentrations of HPβCD in mice following administration by the intrathecal and the intranasal routes showed that in both cases it was taken up by all regions of the central nervous system, albeit the intranasal administration afforded lower levels than those obtained with the intrathecal one [ 72 ].…”