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Intranasal administration offers a nose-to-brain pathway via olfactory and trigeminal routes, reducing systemic exposure. This mini review summarizes pharmacokinetics, efficacy, and translational promise of intranasal iron chelators, comparing them with oral and intravenous routes and highlighting formulation and delivery 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BY  \nVanessa Souza-Mello,  \nRio de Janeiro State University, Brazil  \nREVIEWED BY  \nEduardo Duarte-Silva,  \nUniversity of Texas Health Science Center at Houston, United States  \n*CORRESPONDENCE  \nJonghan Kim,  \n [jonghan_kim@uml.edu](jonghan_kim@uml.edu)  \nRECEIVED 19 September 2025  \nREVISED 27 October 2025  \nACCEPTED 29 October 2025  \nPUBLISHED 18 December 2025  \nCITATION  \nCheng R and Kim J (2025) Intranasal delivery of iron chelators and management of central nervous system disease.  \nFront. Pharmacol. 16:1709259 .  \ndoi: 10.3389/fphar.2025.1709259  \nCOPYRIGHT  \n© 2025 Cheng and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nIntranasal delivery of iron chelators and management of central nervous system disease  \nRuiying Cheng and Jonghan Kim*  \nDepartment of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA, United States  \nBrain iron dyshomeostasis plays a critical role in the pathology of multiple central nervous system (CNS) disorders, including neurodegenerative and neuropsychiatric diseases. Iron chelators such as deferoxamine (DFO) and deferiprone (DFP) have demonstrated therapeutic potential in mitigating disease progression in these conditions. However, systemic administration is hindered by poor blood-brain barrier (BBB) permeability, dose-limiting toxicity, and poor patient compliance due to frequent dosing regimens. In recent years, intranasal (IN) drug delivery has emerged as a promising strategy to bypass the BBB, providing a direct nose-to-brain delivery route via olfactory and trigeminal pathways while minimizing systemic exposure. This review provides a comprehensive summary of the current status of iron chelation therapy for CNS disorders with a focus on pharmacokinetics, efficacy, and translational potential of IN administration. While IN DFO has been extensively studied in preclinical models of Alzheimer’s disease and stroke, recent developments have expanded the scope to other chelators such as DFP. We compare traditional systemic routes, including oral and intravenous, with intranasal administration, highlighting their respective advantages and limitations for CNS delivery. With ongoing advances in formulation and delivery technologies, IN iron chelators provide a promising alternative for the treatment of CNS disorders characterized by impaired iron homeostasis in the brain.  \nKEYWORDS  \niron chelation, intranasal delivery, neurodegenerative diseases, blood-brain barrier, brain delivery  \n1 Introduction  \nNeurological conditions, including central nervous system (CNS) disorders, have emerged as the leading cause of illness and disability worldwide, affecting more than 3 billion individuals – more than one-third of the global population – based on a study in 2021 (GBD, 2021 Nervous System Disorders Collaborators, 2024) . The cases of brain disorders by 2050 are projected to have a 22% increase from 2021 estimates, with the most prevalent conditions being migraine, Alzheimer’s disease, depressive and anxiety disorders, and strokes (Lei and Gillespie, 2024) .  \nDisrupted iron homeostasis in the brain has been increasingly implicated in the pathology of many CNS diseases, where excessive iron accumulation can lead to oxidative stress, neuroinflammation, and ferroptotic cell death in vulnerable brain regions (Salvador et al., 2010) . Therefore, iron chelators have been investigated as potential therapeutic agents to mitigate the iron-related neurotoxic conditions.  \nFrontier","cbCaisuYGn2AXUN9","https://ap.wps.com/l/cbCaisuYGn2AXUN9","pdf",1528148,16,"English","# 1 Introduction\n## Background and global burden of CNS disorders\n## Role of brain iron dyshomeostasis\n## Blood-brain barrier constraints and drug delivery approaches","[{\"question\":\"Why is brain iron dyshomeostasis important in CNS disorders?\",\"answer\":\"Disrupted iron homeostasis contributes to oxidative stress, neuroinflammation, and ferroptotic cell death in vulnerable brain regions.\"},{\"question\":\"What main limitations affect systemic delivery of iron chelators to the CNS?\",\"answer\":\"Systemic administration is limited by poor blood-brain barrier permeability, dose-limiting toxicity, and poor patient compliance due to frequent dosing.\"},{\"question\":\"How does intranasal delivery help overcome the blood-brain barrier?\",\"answer\":\"Intranasal delivery provides a direct nose-to-brain route through olfactory and trigeminal pathways while minimizing systemic exposure.\"}]","Intranasal delivery of iron chelators and management of central nervous system disease | PDF",1790588067]