Brain-targeted intranasal delivery of biologics: a perspective for Alzheimer's disease treatment

Abstract

Alzheimer's disease (AD) presents significant clinical challenges due to its complex pathology and the limitations of traditional drug delivery routes, which often fail to transport therapeutic agents effectively across the blood–brain barrier (BBB). This review focuses on the potential of intranasal drug delivery to enhance therapeutic efficacy in AD treatment by providing a direct route to the central nervous system (CNS). It examines the mechanisms of intranasal administration, including the olfactory and trigeminal pathways, which facilitate rapid drug absorption and distribution to the brain. Additionally, the advantages of intranasal delivery in improving drug bioavailability, reducing systemic side effects, and enhancing patient compliance are discussed alongside innovative formulation strategies, including lipid nanoparticles and other carrier systems. Despite promising outcomes, challenges such as variability in absorption efficiency and the influence of repeated administration remain critical considerations. Furthermore, this review also surveys the current landscape of research for intranasal drug delivery in AD, integrating imaging technologies, emphasizing ongoing studies and future directions for this promising approach. By synthesizing recent findings, this review aims to provide a comprehensive exploration of the interplay of biologics, intranasal delivery, and brain disorders, offering valuable perspectives into the potential of intranasal gene therapy as a potent drug delivery system for CNS diseases.