Molecular insights, challenges and progressions of polysaccharide and protein-based biopolymeric carriers for intranasal drug delivery: A review

The precise targeting of drug molecules to their site of action remains a critical unmet need in pharmaceutical and biomedical science. The nasal route, with its high vascularity, large surface area, and epithelial permeability, enables rapid absorption and has emerged as a promising non-invasive alternative administration pathway for drugs with low oral bioavailability and for sensitive biomolecules such as proteins, peptides, steroids, and vaccines. However, due to several factors including limitation of drug molecular weight, nasal physiology, enzymatic degradation, mucociliary clearance, limited dose, rapid absorption and clearance, nasal routes face challenges for targeted delivery. Compared to conventional polymers, biopolymers have emerged as they are biodegradable, biocompatible, non-toxic, non-immunogenic, prolongs blood circulation, and improves drug loading capacity for both macro and micro-sized molecules. This review summarizes the key biological, physicochemical, and device-related factors governing drug and biomolecule permeability across the nasal mucosa. Additionally, we have discussed the physicochemical, mechanical, and biological fate of various biopolymers and have highlighted recent advances in biopolymer-based nasal delivery systems. Moreover, emphasis is placed on polysaccharide- and protein-based biopolymeric systems specifically tailored to enhance biomacromolecule trafficking through nasal tissues toward both central nervous system and systemic targets.