pH-Responsive Inulin–Sodium Alginate Hydrogel Beads for Sustained Oral Delivery of Bacterial Serine Protease

To overcome the limitations of conventional therapies, targeted delivery of therapeutic interventions is crucial. Specifically, novel hydrogels maximize efficacy while minimizing the premature degradation of therapeutic enzymes. Therefore, the present study aimed to evaluate a developed pH-responsive inulin–sodium alginate (Na+ alginate) hydrogel bead system for colon-specific release of serine protease. Scanning electron microscope (SEM) images revealed structural differences between blank and encapsulated hydrogel beads. Fourier transform infrared spectroscopy (FTIR) spectra further confirmed the successful encapsulation of the bacterial serine protease in inulin-Na+ alginate (IN-Na+ Alg-SP). Thermogravimetric analysis (TGA) confirmed the thermal stability of hydrogel beads over a wide temperature range. Fabricated IN-Na+ Alg hydrogel beads displayed an entrapment efficiency of 54 ± 0.99% with an apparent activity of 260 U/mL. In vitro studies confirmed pH-responsive release with minimal release at pH 1.2 and sustained release at pH 7.4 over 4 h and 30 min. The ex vivo intestinal study confirms that the developed hydrogel has excellent potential as an oral colon-targeted drug delivery system for therapeutic enzymes. The release data best fit the second-order and Korsmeyer–Peppas models (R2 > 0.96), indicating a combination of diffusion and erosion-controlled release mechanisms. These findings suggest that inulin-Na+ alginate hydrogels provide a promising carrier system for colon-specific delivery of serine protease with potential applications in targeted protein digestion and therapeutic interventions.