Coacervate-directed synthesis of CaCO₃ microcarriers for pH-responsive delivery of biomolecules

We report the synthesis of pH-responsive microcarriers via the combination of complex coacervation and mineralization of calcium carbonate (CaCO₃). Positively and negatively charged proteins (bovine serum albumin (BSA) and lysozyme (LSZ)) form electrostatic complexes with poly(acrylic acid) sodium salt (PAANa) and calcium ions in an aqueous solution, leading to the formation of spherical coacervate droplets. By the addition of sodium carbonate, the protein-loaded droplets are mineralized into stable CaCO₃ microcarriers. Since this inorganic material exhibits high solubility in acids, the release of protein from the carriers can be controlled via the pH of the environment. The process results in the successful generation of bulk amounts of monodisperse and colloidally stable microspheres with diameters as small as 300 nm. As the entire synthesis takes place under aqueous conditions, coacervate-directed encapsulation is suitable for sensitive active agents. Accordingly, the method presents a promising approach to synthesize pH-responsive microcarriers for drug delivery applications.