Biopolymeric Chitosan Nanoparticles for Enhanced Stability and Delivery of Omeprazole Magnesium in Acidic Environment

ABSTRACT Chitosan nanoparticles (CSNPs) and chitosan–omeprazole magnesium nanocomposites (CSNCs) were fabricated via ionic gelation to enhance the stability, gastric protection, and therapeutic efficacy of acid‐labile omeprazole magnesium (Ome‐Mg). The formulation achieved high encapsulation efficiency (97 ± 3.5%), with dynamic light scattering (DLS) showing an average size of 42.92 nm and a zeta potential of −26.7 mV, confirming good colloidal stability. Scanning electron microscopy (SEM) revealed porous, sponge‐like particles (∼29 nm, ImageJ), while energy‐dispersive X‐ray spectroscopy (EDX) confirmed Mg, S, F, and P, validating drug incorporation. Fourier‐transform infrared (FTIR) spectra showed characteristic band shifts, indicating hydrogen bonding and electrostatic interactions between chitosan and Ome‐Mg. Powder X‐ray diffraction (PXRD) revealed reduced crystallinity, while thermogravimetric analysis (TGA) demonstrated enhanced thermal stability compared to the pure drug. In vitro assays showed significant, dose‐dependent nitric oxide inhibition in LPS‐stimulated RAW 264.7 macrophages, supporting potential in inflammation‐associated gastric disorders. Drug release in simulated gastric fluid (pH 1.2) displayed sustained biphasic release, nearing completion within 12 h. Kinetic analysis best fit the Michaelis–Menten model ( R 2 = 0.9663), indicating diffusion‐ and erosion‐controlled release. These findings highlight CSNCs as a pH‐responsive, mucoadhesive nanocarrier for effective oral delivery of Ome‐Mg.