Title : Electrospun mucoadhesive nanofiber platform incorporating functionalized gold nanorods for nose to brain drug delivery
Abstract:
The development of effective strategies for central nervous system (CNS) drug delivery remains a major challenge due to the presence of the blood brain barrier and the limited bioavailability of many therapeutic compounds. Intranasal administration has emerged as a promising non invasive approach capable of bypassing the blood brain barrier through direct nose to brain pathways. In this context, electrospun nanofibers represent an attractive platform due to their high surface area, tunable physicochemical properties, and potential mucoadhesive behavior.
This work describes the development and physicochemical characterization of a mucoadhesive electrospun nanofiber platform incorporating gold nanorods functionalized with the D3 peptide (AuNRs-D3) for intranasal drug delivery applications. Systems based on gold nanorods functionalized with D3 have been reported to interact with β-amyloid aggregates and promote anti aggregation and disaggregation effects, positioning them as promising candidates for therapeutic strategies targeting neurodegenerative diseases such as Alzheimer’s disease. Gold nanorods were synthesized through a seed-mediated growth method and subsequently functionalized by PEGylation and conjugation with the D3 peptide. UV–Vis spectroscopy confirmed the preservation of the characteristic longitudinal localized surface plasmon resonance (LSPR) band in the near-infrared region, with a plasmon band centered approximately between 1000 and 1100 nm following surface functionalization. Morphological analysis revealed nanorods with average longitudinal
dimensions close to 60 nm and transverse dimensions near 8–9 nm, corresponding to an aspect ratio favorable for near-infrared applications.
The functionalized nanorods were incorporated into electrospun polymeric matrices based on chitosan and polyethylene oxide (PEO), aiming to obtain nanofibers with suitable physicochemical and mucoadhesive properties for nasal administration. Chitosan was selected due to its cationic character, mucoadhesive behavior, and ability to transiently modulate epithelial tight junctions.
This platform represents a promising strategy for the development of advanced nose to brain nanosystems combining nanotechnology, mucoadhesive biomaterials, and electrospinning technology. Ongoing studies are focused on evaluating swelling behavior, drug release kinetics, mucoadhesion, and in vitro permeability using nasal epithelial cell models.

