Rapidly Gelled pH-Responsive Hydrazone Chitosan–Gelatin–Pectin Hydrogels for Sustained Colonic BBH Delivery

This study presents a pH-responsive hydrogel based on dynamic hydrazone bonds was developed using chitosan, gelatin, and pectin for oral sustained drug delivery. The hydrogel formed rapidly under mild conditions (<5 s for B3 and B5) and showed high water content (∼90%). It degraded slowly in PBS and trypsin but was selectively degradable in pectinase-containing media, adapting to intestinal environments. With BBH as a model drug, all hydrogels achieved >99% encapsulation efficiency (B3: 99.77%; B4: 99.13%). Drug release was well-controlled in gastric fluid (<50% in 2 h for B3) and sustained in colonic fluid (57.93% over 60 h), following Fickian diffusion (Peppas–Sahlin model, R2 > 0.98, k1 ≫ k2). The hydrogels also exhibited strong antioxidant activity (DPPH scavenging >60%, up to 75% for B2) and low hemolysis ratios, indicating excellent biocompatibility. Overall, the hydrogel demonstrates rapid gelation, high drug loading, pH-responsive sustained release, and biosafety, making it a strong candidate for colon-targeted oral delivery.