Organocatalytically-Tuned In Situ Formed Alginate Hydrogel Enables Sustained Therapeutic Release

In situ hydrogelation of alginate represents a versatile strategy for biomaterial design, enabling gel formation directly under physiological conditions without external triggers. In this study, oxidized alginate (Alg-O) was covalently crosslinked with guanidine hydrazide (GH) through acid-catalysed hydrazone linkages to yield stable Alg-Gl hydrogels at ambient conditions. Systematic evaluation of gelation parameters demonstrated that both pH and organocatalyst selection modulate gelation kinetics and minimum gelation concentration, with mildly acidic environments and anthranilic acid catalysis accelerating crosslinking and generating denser network structures. Anthranilic acid catalysis further enabled efficient Alg-Gl hydrogelation at neutral pH, addressing common limitations of hydrazone chemistry under physiological conditions. The dynamic covalent network permitted encapsulation of sensitive therapeutic payloads such as Vitamin B₁₂ without compromising cargo integrity or bioactivity. Alg-Gl hydrogels exhibited sustained, biphasic VB₁₂ release with reduced initial burst and prolonged release compared to conventional alginate matrices. These findings highlight the potential of organocatalytically modulated Alg-Gl hydrogels as a platform for controlled drug delivery and broader biomedical applications, including responsive therapeutics and tissue engineering scaffolds.