Abstract

Organohydrogels (OHG) integrating hydrophilic and hydrophobic domains are emerging as versatile platforms for drug delivery, particularly for poorly soluble antimicrobial agents. In this study, we developed a series of amphiphilic OHG based on poly(acrylic acid) crosslinked with N,N '-methylenebisacrylamide and reinforced with guar gum, incorporating increasing proportions of sesame oil as the hydrophobic phase. The structural, physicochemical, mechanical, and biological impacts of oil incorporation were systematically evaluated. FTIR confirmed successful integration of sesame oil, while SEM revealed a transition from well-defined porous hydrogel networks to denser, heterogeneous architectures as oil content increased. Swelling and gel mass fraction analyses demonstrated that sesame oil modulates solvent uptake, producing a threshold effect at high oil concentrations that enhanced stability in ethanol-water mixtures. Rheological measurements showed increased viscosity and structural robustness in oil-containing formulations. Constitutive antibacterial tests indicated concentration-dependent inhibition of Staphylococcus aureus, consistent with the known bioactivity of sesame oil. Drug release assays using doxycycline, norfloxacin, and cloxacillin revealed that the highest-oil organohydrogel (p(AA)-MBA-GG-SES3) significantly slowed diffusion, enabling sustained antibiotic release compared to the rapid release observed in oil-free hydrogels. Correspondingly, antibacterial activity from release aliquots demonstrated prolonged inhibition for SES3 systems. Overall, these sesame-oil-based OHG exhibit tunable physicochemical behavior and enhanced capacity for sustained antimicrobial delivery, highlighting their potential in localized infection management.