A comprehensive review on natural polysaccharides based in situ gels for nasal drug delivery.

In situ nasal gels developed from natural polysaccharides have been recognized as a highly promising drug delivery system for the effective treatment of both systemic and localized diseases. These gels are triggered to undergo sol-to-gel transition when exposed to nasal physiological parameters like temperature, pH, or ionic strength, facilitating increased mucoadhesion, extended residence time, and enhanced bioavailability of drugs. Biocompatible and biodegradable natural polysaccharides such as chitosan, gellan gum, alginate, and pectin are the most commonly used natural polymers. The gelation mechanisms include, gelation triggered by ionic stimuli, pH stimuli, temperature stimuli, and by enzymatic crosslinking. In situ gels are mainly characterized by rheological behavior and textural analysis ensuring their performance. Besides, a 3D-printed human nasal cavity model can be used for deposition and biocompatibility studies. These in situ gels are notably useful for controlled delivery in allergic rhinitis, sinusitis, central nervous system diseases (e.g., epilepsy, migraine), and even systemic disorders in need of avoiding first-pass metabolism. This review emphasizes the state-of-the-art developments in natural polysaccharide-based in situ nasal gels in their design, action, and applications, based on their usefulness in revolutionizing nasal drug delivery as a novel, more effective, and friendly therapeutic approach to patients.