Four ordered mesoporous silica supports with different pore structure characteristics were investigated for their drug loading and release abilities with regard to their structural variabilities as well as implications of surface modification. The (model) drug molecule in question was the poorly water-soluble glucocorticoid Prednisolone, composed of a steroid skeleton with functional groups in the form of carbonyls and hydroxyls. Under non-aqueous conditions, such as those applied for drug loading, these functional groups are expected to interact with the surface silanols of the silica supports, but this interaction could possibly also be enhanced by introducing amino groups to the silica surfaces. Thus, all four supports were further functionalized by surface hyperbranching of polyethyleneimine), PEI, which was successfully incorporated to all supports in high amounts (> 30 wt%). However, the accessibility of the pore system after organic modification was dependent on the pore sizes and structures, highlighting the importance of using large-pore mesophases with adequate structures when aiming for applications involving (bulky) guest molecules. Additionally, after incorporation of large amounts of guest molecules (40 wt%), full water accessibility was retained in that the loaded cargo could be rapidly released from the carrier matrixes, which is a crucial requirement when formulating poorly soluble substances. Results displayed that the release of Prednisolone from the silica supports occurred faster than the dissolution of the pure drug. All silica materials released more than 85 % of the adsorbed drug in 5 h, independently of the support material. Thus, the confinement of Prednisolone inside the mesopores seems to be the main reason for the faster kinetic release rate. These constraints imply that Prednisolone becomes more mobile inside the pores, and therefore more soluble in release medium. These results confirm the potential of silica supports as drug delivery carriers for drugs with limited water solubility such as steroids.