Controllable Synthesis of Calcium Carbonate with Different Geometry: Comprehensive Analysis of Particle Formation, Cellular Uptake, and Biocompatibility

Carefully designed micro- and nanocarriers can provide significant advantages over conventional macroscopic counterparts in drug delivery applications. For the successful delivery of bioactive compounds, carriers should possess a high loading capacity, triggered release mechanisms, biocompatibility, and biodegradability. Porous calcium carbonate (CaCO₃) is one of the most promising platforms, which can encompass all the aforementioned requirements. Here, we study both the formation of particles and the biological applicability of CaCO₃. In particular, differently shaped anisotropic CaCO₃ particles are synthesized using a sustainable and green approach based on coprecipitation of calcium chloride and sodium carbonate/bicarbonate at different ratios in the presence of organic additives. The impact of salt concentrations, reaction time, and organic additives are systematically investigated to achieve a controllable and reliable design of CaCO₃ particles. It is demonstrated that the crystallinity (vaterite or calcite phase) of particles depends on the initial salt concentrations. The loading capacity of prepared CaCO₃ particles is determined by their surface properties such as specific surface area, pore size, and zeta-potential. Differently shaped CaCO₃ particles (spheroids, ellipsoids, and toroids) are exploited, and their uptake efficiency on an example of C6 glioma cells is evaluated. The results show that ellipsoidal particles are more likely to be internalized by cancer cells. All the particles tested are also found to have good biocompatibility. The ability to design physicochemical properties of CaCO₃ particles has a significant impact on drug delivery applications since particle geometry substantially affects cell behavior (internalization and toxicity).