Advances in mucoadhesive and mucus-penetrating materials, nano-formulations, and in situ gelling systems for nasal drug delivery

Introduction Intranasal drug delivery is increasingly valued not only for local therapy but also as a noninvasive route that can bypass the blood – brain barrier, enabling rapid treatment of neurological and systemic diseases. However, mucociliary clearance and limited epithelial absorption often reduce residence time and bioavailability, creating a need for more effective formulation strategies. Mucoadhesive and mucus-penetrating systems are among the most promising approaches.Areas covered This review summarizes nasal anatomical and physiological features that govern interactions between formulations and the mucosa. It overviews representative intranasal dosage forms (liquids, powders, gels, films, in situ gelling systems, and nano-formulations). Polymers used as mucoadhesive agents are classified into first- and second-generation materials, which enhance adhesion through hydrogen bonding, electrostatic interactions, or covalent attachment. The review also highlights polymers applied to nanoparticle surfaces to facilitate diffusion through mucus and improve epithelial access. Finally, methods to evaluate mucoadhesion and toxicity are outlined, including alternative in vitro and in vivo models.Expert opinion Recent advances have expanded nasal delivery options, particularly for nose-to-brain targeting. Yet translation remains limited by insufficient validation, long-term safety uncertainties, and repeated-dose effects. Future progress requires balancing adhesion with penetration, robust toxicology, and integration of innovative polymers with optimized devices.