Controllable synthesis of calcium carbonate with different geometry: comprehensive analysis of particles formation, their cellular uptake and biocompatibility

Carefully designed micro and nanocarriers can provide significant advantages over conventional macroscopic counterparts in biomedical applications. The set of requirements including a high loading capacity, triggered release mechanisms, biocompatibility, and biodegradability should be considered for the successful delivery realization. Porous calcium carbonate (CaCO3) is one of the most promising platforms, which can encompass all the beforehand mentioned requirements. Here, we study both the particles formation and biological applicability of CaCO3. In particular, anisotropic differently shaped CaCO3 particles were synthesized using green sustainable approach based on co-precipitation of calcium chloride and sodium carbonate/bicarbonate at different ratios in the presence of organic additives. The impact of salts concentrations, reaction time, as well as organic additives was systematically researched to achieve controllable and reliable design of CaCO3 particles. It has been demonstrated that the crystallinity (vaterite or calcite phase) of particles depends on the initial salts 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, toroids) were used to evaluate their uptake efficiency on the example of C6 glioma cells. The results show that the ellipsoidal particles possess a higher probability for internalization by cancer cells. All tested particles were also found to have a good biocompatibility. The capability to design physicochemical properties of CaCO3 particles has a significant impact on drug delivery applications, since the particles geometry substantially affects cell behavior (internalization, toxicity) and allows outperforming standard spherical counterparts.