In Situ Gels for Nasal Delivery: Formulation, Characterization and Applications

The nasal route offers many advantages for drug delivery: quick onset of action, better patient compliance, avoidance of first-pass metabolism and bypassing the blood-brain barrier. Despite the potential of this route, several challenges exist, such as the short drug retention time caused by mucociliary clearance (MCC). In situ forming gels, which undergo a sol-to-gel transition with specific triggers at the site of action, present real opportunities in this field. They combine the intrinsic characteristics of hydrogels (elasticity and water-holding capacity) with responsiveness, allowing easy application of drugs (spraying or extruding through a nozzle), as well as prolonged retention in the nasal cavity. The incorporation of mucoadhesive polymers, additives and nanocarriers can further tune the properties of in situ gels as nasal delivery platforms. This review summarizes advances in in situ gels for nasal drug delivery. We first describe challenges of the nasal route, target properties of in situ nasal gels, and then present both “classic” gelling polymers (poloxamers and polysaccharides) – which form the bulk of reported studies on nasal gels – as well as novel bespoke materials; we review characterization methods, highlighting the lack of standardization and accepted target values, then discuss applications by spraying, and conclude with future prospects.