Next-generation intranasal delivery nano-platforms for targeted brain therapy of Alzheimer’s disease

Abstract

Introduction: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that poses a growing global health burden. Effective drug delivery to the brain is largely constrained by the selective nature of the blood–brain barrier (BBB), which limits therapeutic efficacy of conventional oral medications. Intranasal administration has emerged as a noninvasive and promising route for direct nose-to-brain transport, circumventing BBB restrictions. Area covered: This review explores the potential of intranasal drug delivery as an alternative approach for targeted brain therapy in Alzheimer’s disease. It comprehensively discusses the mechanisms of nasal absorption, physiological and formulation-related barriers, and the role of advanced nanocarrier platforms in overcoming these limitations. Emphasis is placed on recent innovations involving polymeric, lipid-based, and vesicular carriers, along with the incorporation of mucoadhesive and permeation-enhancing agents. Expert opinion: The present focus is enhancing bioavailability, prolonging drug residence time, and minimizing systemic toxicity. Surface modifications of nanocarriers further facilitates mucosal adhesion and enables effective nose-to-brain transport of encapsulated therapeutic agents. However, clinical translation remains challenging due to interindividual variability in nasal physiology, scalability constraints, and regulatory complexities. Future progress will depend on the rational design of multifunctional nanocarriers, integration of mucoadhesive and stimuli-responsive components, and the use of precision-based formulation strategies.