Design and Optimization of Brain-Targeted Nasal Liposomes for Enhanced Delivery of Galantamine

Abstract

The present study demonstrates the potential of intranasal liposomal delivery of galantamine as an advanced therapeutic strategy for vascular dementia (VaD). Conventional routes of galantamine administration, including oral and intravenous delivery, are limited by low bioavailability, systemic side effects, and poor blood–brain barrier penetration. In contrast, liposomal encapsulation significantly enhanced stability, entrapment efficiency, and sustained release of galantamine, ensuring higher brain concentrations. Ex-vivo and in-vivo studies confirmed improved permeation through the nasal mucosa and efficient targeting of brain regions implicated in cognitive decline. The optimized formulation (F3) achieved the highest drug targeting efficiency and direct transport percentage, highlighting its superiority in nose-to-brain delivery. Behavioral studies further validated enhanced cognitive performance, consistent with the cholinergic hypothesis underlying VaD pathology. Safety evaluations showed intact nasal mucosa, high cell viability, and absence of behavioral abnormalities, confirming the biocompatibility of liposomal formulations. Importantly, this approach addresses a major gap in dementia therapeutics by specifically focusing on VaD, which has been overshadowed by Alzheimer’s disease in drug delivery research. Overall, the findings emphasize that intranasal liposomal galantamine offers a non-invasive, patient-friendly, and efficient drug delivery system with strong translational potential for dementia management. In conclusion, intranasal liposomal galantamine represents a novel, efficient, and safe therapeutic strategy for vascular dementia, with the potential to redefine management of cognitive disorders by integrating advanced nanotechnology with patient-centered care.