Study On The Preparation And Drug Loading Properties Of Amorphous Calcium Phosphate Nanoparticles

Amorphous calcium phosphate?ACP?has attracted extensive attention from scholars at home and abroad owing to its good pH sensitivity,biocompatibility,biodegradability and large specific surface area.However,ACP is a metastable phase,which is prone to transform into crystalline phase,and has poor dispersibility in solution,resulting in a great limitation in the application of drug carrier.Therefore,ACP nanoparticles were modified by Casein,hyaluronic acid?HA?and sodium hexametaphosphate??NaPO₃?₆?in this paper.And curcumin?Cur?,a tumor drug model,was encapsulated by ACP nanoparticles to improve poor chemical stability and rapid release of Cur in vivo.The specific research contents are as follows:1)ACP nanoparticles were prepared by coprecipitation method.The effects of reaction concentration,pH,temperature and time on the crystal phase of the samples were investigated by single factor experiment.At the same time,ACP nanoparticles were characterized by Fourier transform infrared spectroscopy?FTIR?,scanning electron microscopy?SEM?.The results show that ACP was obtained at pH 8,the concentration of PO₄^3-0.024 mM,30oC for 10 min.The prepared ACP nanoparticles under the optimal conditions were spherical particles,and had relatively high specific surface area.Meanwhile,the average particle size and pore diameter were 100 and 10.5 nm,respectively.In addition,ACP nanoparticles were efficient for drug loading and pH response release,and exhibited excellent abilities to scavenge free radicals and inhibit A549 cells.2)Casein-ACP,HA-ACP nano-composite particles were prepared using Casein and HA as stabilizers.The effects of Casein and HA concentrations on the crystal phase of the products were investigated by X-ray diffractometry?XRD?,and the nano-composite particles were characterized by FTIR and SEM.The results show that the prepared sample was ACP nano-composite particles when the concentrations of Casein and HA were 2 and 1 mg/mL,respectively.The nano-composite particles did not change much in particle size for the two stabilizers,were spherical particles with particle size of 100 nm,and had agglomeration phenomenon.They maintained their amorphous nature for at least 3 months in the presence of two stabilizers.The MTT test results show that the Casein-ACP,HA-ACP nano-composite particles had good biocompatibility,and the Cur-Casein-ACP,Cur-HA-ACP nano-composite particles had better anti-tumor ability in vitro.3)The Casein-ACP,HA-ACP nano-composite particles were modified with?NaPO₃?₆,and Casein-ACP-?NaPO₃?₆,HA-ACP-?NaPO₃?₆ nanocomposite particles with good dispersibility were obtained.The structure,particle size distribution and dispersion stability of the nano-composite particles were analyzed by XRD and FTIR.The results show that the nano-composite particles had good dispersion stability in aqueous solution when the mass ratio of Casein-ACP,HA-ACP and?NaPO₃?₆ was 1:4,and the dispersion kept stable for one month at room temperature.The?NaPO₃?₆ modified nano-composite particles still maintained an amorphous phase,and the particle size did not change much compared with that before modification,which was 280 and 254 nm,respectively,and the distribution was narrow.Meanwhile,Cur-Casein-ACP-?NaPO₃?₆,Cur-HA-ACP-?NaPO₃?₆ nano-composite particles had high drug loading,release and in vitro anti-tumor ability.In summary,this paper obtained the Casein-ACP-?NaPO₃?₆,HA-ACP-?NaPO₃?₆ nano-composite particles with long storage stability time and good dispersion stability,which proved that the carrier had high drug-loading capacity,and pH response release properties,and the drug-loading nanoparticles had good anti-tumor ability.The research work has greatly expanded the applications of ACP in food and biomedical fields.