Numerous drawbacks in the current medical treatment of chronic inflammations still require the design of sensitive and gentle methods without side effects. Layer-by-layer (LbL) coated microcarriers loaded with a cocktail of anti-inflammatory substances are supposed to be a new challenge for the medical treatment of immunoreactive cells such as macrophages and polymorphonuclear leukocytes (PMN). Nevertheless, microcarrier application requires biocompatibility of the system itself. Therefore, the aim of this study was to investigate microcarrier CaCO3 systems LbL coated with biopolymers and a lipid bilayer, respectively, regarding the maintenance of the release of pro-inflammatory cytokines as TNF alpha and IL1 beta at normal levels. Only marginal increases after microcarrier interaction were allowed. The required microcarrier optimization results in the maximum use of a carrier/cell ratio of 1 : 1 for biopolymer-coated carriers and a carrier/cell ratio up to 5 : 1 for lipid-bilayer-coated carriers during the coincubation with macrophage-like cells. Low formation of reactive oxygen species (ROS) could not be maintained by either reduced carrier/cell ratios or by a surface lipid bilayer.