A review on chitosan-based delivery systems for vitamin B12: Advances, challenges, and future prospects

Chitosan, a cationic biopolymer derived from chitin, has gained significant attention as a multifunctional carrier for Vitamin B12 delivery, offering advantages in overcoming physiological and formulation-related barriers. This review explores chitosan's mucoadhesive properties, driven by electrostatic interactions with mucosal glycoproteins, which enhance mucosal residence time and facilitate paracellular transport by reversibly modulating epithelial tight junctions enabling intrinsic factor-independent absorption of hydrophilic compounds such as Vitamin B12. Additionally, chitosan protects Vitamin B12 from acidic and enzymatic degradation during gastrointestinal transit, maintaining its structural integrity and bioactivity. The review discusses various chitosan-based platforms nanoparticles, hydrogels, and chemically modified derivatives like trimethyl and carboxymethyl chitosan used across oral, nasal, buccal, injectable, and transdermal routes. These systems demonstrate improved bioavailability, controlled release, and targeted delivery. Notably, chitosan nanoparticles enhance oral absorption, while hydrogel formulations offer sustained release. Recent developments in stimuli-responsive systems represent an exciting direction for site-specific, regulated release. However, this review also highlights critical challenges, including long-term safety, immunogenicity, and pharmacokinetic profiling, especially under chronic use or via novel routes like nose-to-brain delivery. Overall, this review provides insights into current advances and translational prospects of chitosan-mediated Vitamin B12 delivery systems in food and pharmaceutical applications.