pH-responsive chitosan-alginate hydrogel beads: for enhanced bioavailability and controlled release of omeprazole

To develop a pH-responsive drug delivery using chitosan-alginate hydrogel beads for enhanced therapeutic efficacy of omeprazole.

The developed system offers improved drug entrapment, release profiles, and enhanced bioavailability for omeprazole compared to commercial formulation.

pH-responsive chitosan-alginate hydrogel beads were prepared using a modified ionotropic gelation technique. The process was optimized via a two-level factorial design. Characterization involved drug entrapment efficiency determination, molecular dynamic simulations, in vitro drug release studies, and Caco-2 cell monolayer permeability assessments. Stability was evaluated under accelerated conditions, and in vivo efficacy was tested in rats with indomethacin-induced peptic ulcer disease.

The optimized formulation achieved 82.70 ± 2.02% drug entrapment efficiency. In vitro release studies demonstrated superior pH-dependent behavior, with minimal release (<20%) at pH 1.2 and sustained release (>92%) at pH 7.4 over 24 h. Molecular modeling revealed high entrapment efficiency. The Caco-2 cell study showed a 2-fold increase in drug permeability (2.8 × 10^-6cm/s) compared with that of free omeprazole (4.5 × 10^-6cm/s) and a commercial formulation (3.7 × 10^-6cm/s), with no significant cytotoxicity (cell viability > 95%). In vivo studies demonstrated significant ulcer healing, reducing the ulcer index from 3.96 to 1.20. Accelerated stability studies indicated a 24-month shelf-life under normal conditions.

The novel chitosan-alginate hydrogel system offers a promising solution for improving omeprazole delivery, with significant enhancements in drug entrapment, release profile, bioavailability, and stability.