Calcium carbonate is an important chemical material with abundant raw materials, simple production process and excellent application performance. It is widely used in rubber, ink, medicine, food and other fields. In the field of medicine, calcium carbonate is more widely used. Calcium carbonate itself is an excellent calcium source additive and supplement. Calcium carbonate, as the main ingredient of calcium supplement drugs, has high calcium content, good absorption and high bioavailability. Pharmaceutical calcium carbonate can be used as a base material and filler for some medicinal materials, and can also be used to prepare fermentation culture matrix. It not only provides the calcium source required by microorganisms but also maintains the pH stability of the system. It is an indispensable buffer in the biological fermentation process. It is worth noting that calcium carbonate has been used as a typical biomaterial to construct intelligent carriers for the delivery of genes, enzymes and drugs.
There are three main crystal forms of calcium carbonate: calcite, aragonite and vaterite. Among them, vaterite is an orthorhombic crystal with slight differences in unit cell structure from calcite. Because its unit cell structure contains carbonate ions and calcium ions, and the symmetry and orderly arrangement of the unit cell structure make it present a spherical shape. Vaterite calcium carbonate rarely exists in nature. Usually, vaterite is a polycrystalline vaterite composed of nano-sized microcrystalline spherules, rather than a single crystal like calcite and aragonite. In addition, vaterite calcium carbonate also has disc-shaped, flake-shaped, hexagonal, lens-shaped and other morphologies. Spherical vaterite calcium carbonate is considered to be the most promising type of calcium carbonate.
Among the three common crystalline calcium carbonates, calcite is the most thermodynamically stable crystal form, followed by aragonite, while nepheline is an extremely unstable crystal form, which is very easy to transform into thermodynamically stable calcite or aragonite in aqueous solution. Under different environments, adding certain substances can stabilize vaterite and slow down its crystal transformation to calcite. Studies have shown that with the addition of different synthesis conditions, different additives and different post-treatment methods to the synthesis of calcium carbonate, the crystal form of calcium carbonate microspheres becomes controllable. On this basis, the control and selective synthesis of the crystal form of calcium carbonate microspheres can be achieved by adjusting temperature, pH, time and other conditions. Through the analysis of the generation pathway and unit cell structure of vaterite calcium carbonate microspheres, its morphology, size and physical properties can be effectively regulated.
Compared with the other two crystal forms, the vaterite type has conventional properties such as low density, white and odorless, acid decomposable and chemically stable, etc., and also has hollow or porous structure, uniform particle size distribution, micro-nano size, high hydrophilicity, large specific surface area, good solubility and dispersibility, good biocompatibility and safety, good degradability, strong phase change ability, spherical distribution and other characteristics. Therefore, vaterite calcium carbonate has a broad application prospect in inorganic drug carrier materials.
CaCO3 micro-nanoparticles can be used for sustained release of a variety of hydrophilic or hydrophobic drugs. Since CaCO3 degrades slowly in the human body, it can be used as a long-acting drug delivery system to retain drugs in the body for a long time. pH-sensitive PEI-CO2@CaCO3 colloidal particles can bind the reactive groups on vaterite calcium carbonate nanoparticles to the targeting molecules in the target tumor cells, thereby achieving the effect of drug transport and tumor inhibition.
The porous morphology and developed internal structure of vaterite allow it to accommodate molecules of various properties. These particles can effectively capture a variety of bioactive substances, including low molecular weight compounds and macromolecules, and load them into the crystal stone through physical adsorption (diffusion) into the pores or co-precipitation (co-synthesis) during the particle formation process. Vaterite calcium carbonate microspheres with adjustable particle size and pH sensitivity are more suitable for drug and gene delivery.