Development of Microneedles Coated with Bioadhesive Hydrogel for Sustained Drug Delivery in Gastrointestinal Mucosa

Biological macromolecular drugs, such as proteins and peptides, face significant oral bioavailability challenges due to enzymatic degradation, mucosal barriers, and rapid clearance in the gastrointestinal (GI) tract. While micro needle robots offer a promising alternative by directly injecting drugs into the GI mucosa, their efficacy is limited by premature detachment caused by peristaltic forces. This study introduces bioadhesive hydrogel-coated microneedles designed to overcome this limitation. The microneedles were functionalized with a dual-network hydrogel coating synthesized via sequential photo-crosslinking and oxidative polymerization of dopamine, enabling robust adhesion through reversible non-covalent interactions (hydrogen bonding, π-π stacking, and metal coordination) with mucosal tissues. Ex vivo evaluations using chicken tissue demonstrated that the coated microneedles exhibited a 50% retention of initial adhesion energy after eight penetration-withdrawal cycles, significantly outperforming uncoated controls. The hydrogel coating also maintained mechanical resilience under physiological shear stresses and prolonged drug release while ensuring biocompatibility, with no observed tissue damage or inflammatory responses. These findings validate the potential of bioadhesive micro needles to enhance retention and sustained drug delivery in dynamic GI environments. By addressing critical challenges in mucosal adhesion and drug release kinetics, this work advances microneedle robot technology toward clinical applications, offering a transformative platform for oral delivery of biologics in treating chronic diseases. Future efforts will focus on in vivo validation and scalable manufacturing to accelerate translation into therapeutic use.