Intranasal Therapeutics for Brain Aging and Neuroinflammation: Current Evidence, Mechanisms, and Future Clinical Perspectives
Abstract
Brain aging is a progressive biological process associated with structural, functional, and molecular changes that contribute to cognitive decline and increased susceptibility to neurodegenerative disorders. Among the key mechanisms involved, chronic neuroinflammation, oxidative stress, and Blood–Brain Barrier (BBB) dysfunction plays central roles in disease progression. Conventional systemic drug delivery methods often fail to achieve adequate Central Nervous System (CNS) concentrations due to BBB limitations, reducing therapeutic efficacy in age-related neurological conditions. In recent years, intranasal drug delivery has emerged as a promising non-invasive strategy for bypassing the BBB and enabling direct nose-to-brain transport via olfactory and trigeminal pathways.
This review critically evaluates current evidence on intranasal therapeutic approaches targeting brain aging and neuroinflammation. It explores the biological mechanisms underlying neurodegeneration, with emphasis on microglial activation, pro-inflammatory cytokine release, mitochondrial dysfunction, and oxidative injury. Furthermore, it discusses advances in intranasal formulations, including nanoparticles, liposomes, nanoemulsions, and peptide-based delivery systems designed to enhance drug stability, absorption, and brain targeting efficiency.
Preclinical and emerging clinical studies suggest that intranasal administration of neuroprotective agents such as insulin, growth factors, anti-inflammatory compounds, and small molecules may improve cognitive function, reduce inflammatory markers, and modulate neurodegenerative pathways. However, variability in formulation design, dosing strategies, and translational evidence remains a significant challenge.
Overall, intranasal delivery represents a rapidly evolving field with substantial potential for managing brain aging and neuroinflammation. Nevertheless, further well-designed clinical trials are required to establish standardized protocols, long-term safety, and definitive therapeutic efficacy.
