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Ordered Mesoporous Silica (OMS) materials, particularly SBA-15, are widely used in drug delivery due to their structural stability and high porosity. However, the role of macroporosity (pores >50 nm) in influencing protein adsorption and spatial distribution remains poorly understood. In this study, three SBA-15 variants were produced by changing the synthesis temperature and stirring speed, and combined evolved gas analysis (EGA), Raman imaging, and X-ray micro-computed tomography (micro-CT) were used to investigate the adsorption and distribution of lysozyme, a model protein, in the samples. While thermal analysis showed comparable overall protein uptake across all variants, Raman imaging and micro-CT demonstrated that SBA-15 with the larger macropore distribution exhibited a less uniform lysozyme distribution. These observations suggest that macroporosity affects protein localization within SBA-15, which is critical for optimizing antigen delivery and release. Our results advance understanding of how OMS morphology impacts biomolecule encapsulation, offering insights valuable for the design of advanced drug delivery systems and oral vaccines.