Nanostructured Calcium Phosphate Materials: Controlled Synthesis And Drug Delivery Application

The functional nanostructured materials hold the promise for the applications in future clinical treatment to enhance therapeutic efficacy. In the past several decades, various types of nanostructured functional materials have been developed and investigated in the biomedical applications. Calcium phosphate(CaP) has high biocompatibility and can serve as the ideal candidate for functional nanosystems. CaP based nanostructured biomaterials have been studied and applied in many biomedical fields such as bone repair/tissue engineering, drug/gene delivery. This dissertation has given some progress of the controlled synthesis of nanostructured functional CaP materials and their applications in the field of drug delivery.(1) Under microwave-assisted solvothermal condition, a self-assembling structure of hydroxyapatite(HA) microsphere is obtained in water, and an unusual regular polyhedron structure is obtained in presence of ethylene glycol(EG). The solvent of EG has shown effective regulatory action on the chemical phase and structure of the CaP materials. Meanwhile, HA oriented arrays has been prepared using calcium acetylacetonate and creatine phosphate disodium salt tetrahydrate in mixed solvents of deionized water and N,N-dimethylformamide under solvothermal treatment. Creatine phosphate disodium salt tetrahydrate acts as an organic phosphorus source and a soft template for the formation of hydroxyapatite oriented arrays.(2) A facile microwave-assisted liquid phase method has been developed for the preparation of the magnetic nanocomposite materials consisted by HA ultrathin nanosheets and Fe3O4 magnetic nanoparticles(HAPUN/MNs). The HAPUN/MNs nanocomposite shows a property of pH-controlled drug release behavior which can be explained by gradually dissolution of the HA in a low pH environment.(3) A room-temperature solution method has been used for the preparation of multifunctional Eu3+ and Gd3+ dual-doped CaP(Eu3+/Gd3+-CaP) nanospheres in the presence of an amphiphilic block copolymer PLA-mPEG. Under the excitation of a light with wavelength at 470 nm, Eu3+/Gd3+-CaP nanospheres exhibit a strong near-infrared emission at 700 nm in the NIR spectrum. Furthermore, Eu3+/Gd3+-CaP nanospheres can be used as the drug nanocarriers with a high drug loading capacity and ultralong sustained drug release using a model drug of ibuprofen. More importantly, the noninvasive visualization of nude mice with subcutaneous injection indicates that the Eu3+/Gd3+-CaP nanospheres are suitable for the application in in vivo bio-imaging.(4) The CaP material with defined mesoporous structure has been prepared using a phosphate contained natural molecule of adenosine triphosphate(ATP). The average hydrodynamic size, pore size and the values of BET specific surface area of the mesoporous CaP spheres are ranged from 585 nm to 239.7 nm, 17.8 to 10.1 nm and 209 to 315 m2 g-1, corresponding to the doping concentrations of Eu3+ from 0 to 10 %, respectively. The mesoporous CaP has shown pH responsive docetaxel drug release property which attributed to increased dissolution of the mesoporous CaP in acid solution. Furthermore, the Eu3+ doped mesoporous CaP administrated group displayed a clearly distinguished NIR fluorescence signal in vitro and in vivo.