Scalable Synthesis Of Amorphous Calcium Carbonate Nanoparticles And The Application In Drug Delivery

In order to reduce the side effects and improve therapeutic effect, drug delivery systems based on nanomaterials attract many interests because of the controlled location and release of drugs in diseased sites. Among those various nanomaterials, calcium carbonate is advantageous in good biocompatibility, biodegradability, safety and low cost. In addition, calcium carbonate is pH-sensitive; its structure is well maintained in neutral environments, while controlled drug release can be triggered by the acid environment in tumor tissues and lysosomes. Calcium carbonate with the above advantages exhibits great value and potential as drug delivery systems. However, in the current study of controllable synthesis, nanoscale calcium carbonate for the property of its rapid crystallization is difficult to obtain monodispersed and uniform nanoparticles with high-quality, stability and tunable sizes, which is the biggest challenge for calcium carbonate widely used as a biological material.To solve the above problems, there was a comprehensive research on controllable synthesis and drug delivery of amorphous calcium carbonate (ACC). In the presence of several forms of calcium carbonate, ACC is isotropic without specific lattice structure, which results it’s easier to get stable nanoscale materials for drug delivery. We fabricated ACC nanoparticles with high-quality and stability by facile synthesis. After that, these synthetic approaches were used to encapsulate hydrophilic and hydrophobic drugs in ACC nanoparticles via one-step synthesis. The study included following three parts.1. Scalable synthesis of ACC nanoparticles with tunable size, monodispersity, uniformity and stability. By one-step vapor diffusion method, we fabricated pure ACC nanoparticles, and effects of synthesis condition on morphology were investigated, thereby monodispersed and uniform ACC nanoparticles with tunable diameters were prepared. Silica was used as appropriate reagent for surface modification of ACC nanoparticles with different diameters to improve thermodynamic instability that easily leads to rapidly dissolving in an aqueous environment and crystallization.2. Preparation of drug-ACC nanoparticles for water-soluble drugs delivery. The three drugs of indocyanine green, fluorescein isothiocyanate and rhodamine B molecules were encapsulated into ACC nanoparticles via self-assembly process, and loading capacity and availability of the obtained drug-ACC nanoparticles were characterized, respectively.3. Construction of camptothecin @silica nanocarrier system via amorphous calcium carbonate as template. Camptothecin (CPT) molecules with open loop state were encapsulated into ACC nanoparticles by self-assembly process. Then the as-prepared CPT-ACC nanoparticles were coated by silica to form CPT-ACC @ silica nanoparticles. An active CPT @ silica nanocarrier system was finally prepared after CPT molecules were recovered with the lactone ring state in acidic condition.We successfully prepared monodispersed and uniform ACC nanoparticles with high-quality, stability and tunable sizes by further investigating synthetic methods and mechanism. Moreover, these nanoparticles were applied to different drugs delivery to achieve and expand its potential for applications.