Intranasal Drug Delivery Technology in the Treatment of Central Nervous System Diseases: Challenges, Advances, and Future Research Directions

Abstract

As population aging becomes an increasingly critical global issue, the incidence of central nervous system (CNS) diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke, has risen sharply. However, the blood-brain barrier (BBB) presents a significant obstacle to the effective treatment of these CNS disorders, limiting the ability of therapeutic agents to reach the brain. In this context, intranasal drug delivery, which bypasses the BBB, has attracted considerable attention in recent years. By utilizing pathways such as the olfactory and trigeminal nerves, intranasal drug delivery facilitates the rapid transport of drugs to the brain, thereby enhancing both the bioavailability and targeting efficiency of the drugs. This review provides an overview of the molecular mechanisms underlying intranasal drug delivery, its advancements in the treatment of CNS diseases, strategies to improve delivery efficiency, and a discussion of the challenges and potential future directions in this field. The aim of this paper is to offer valuable insights and guidance for researchers and clinicians working in the area of CNS disease treatment.

Keywords: Alzheimer’s disease; blood–brain barrier; central nervous system; hydrogels; intranasal drug delivery; nanotechnology; olfactory nerve pathway; small molecules; trigeminal nerve pathway.

Figure 1

This illustration shows various central nervous system diseases that can be treated via intranasal drug delivery, including Alzheimer’s disease, Parkinson’s disease, meningitis, ischemic stroke, hemorrhagic stroke, and other unspecified diseases. The areas marked by red stars or indicated by arrows represent the sites of tissue damage or functional loss. (all or parts of the figures were created using Servier Medical Art (https://smart.servier.com/), accessed on 5 April 2025, licensed under CC BY 4.0.).

Figure 2

This illustration depicts the mechanisms of intranasal drug delivery. The therapeutics can be transported from the nose to the brain through the olfactory and trigeminal nerves and vascular transport across the BBB. The primary routes for nose-to-brain transport are olfactory and trigeminal nerve pathways (all or parts of the figures were created using Servier Medical Art (https://smart.servier.com/), accessed on 5 April 2025, licensed under CC BY 4.0.).

Figure 3

The diagram illustrates different types of drugs that can be delivered via the intranasal route, including exosome-derived drugs, cell-derived drugs, drug delivery systems, chemical drugs (in the form of solutions or dispersions), biological drugs, and nucleic acid drugs (all or parts of the figures were created using Servier Medical Art (https://smart.servier.com/), accessed on 5 April 2025, licensed under CC BY 4.0.).