Preparation Of Ordered Porous Hydroxyapatite And Analysis Of Drug Delivery Factors

Drug delivery system can greatly alleviate the sudden release phenomenon after taking the drug to improve the effective release efficiency,which reduces the drug concentration in blood,resulting in reducing the negative effect of the drug on the human body.Among,due to the excellent biocompatibility,biological activity and bio-absorbability of hydroxyapatite(HA),it is showed a great range of applications in the drug delivery system as a carrier of drugs.Drug delivery properties of HA could be improved by preparing into the ordered porous structure and doping,showing great drug loading and drug release performance,which made release durability better and slowed the sudden release of drugs.HA with these properties will be more widely used in the drug delivery system.In this thesis,the preparation process and drug delivery properties of ordered porous HA were studied.Moreover,ordered porous HA was modified with doping Zn and Mg or co-doping,of which the drug delivery properties and mechanisms were studied.(1)Polystyrene microsphere emulsions with uniform size of 380±10 nm were prepared by soap-free emulsion polymerization,then polystyrene colloidal crystal templates were prepared by evaporation self-assembly method,of which the morphology was characterized.Ordered porous HA was prepared by the colloidal crystal template method,then effects of the mass ratio of template and precursor,the impregnation process,and the type of precursor dispersant on the morphology as well as phase and drug delivery properties of ordered porous HA were investigated.The results showed that polystyrene colloidal crystal templates prepared by the evaporation self-assembly method were arranged neatly and orderly.Effects of the mass ratio of the template and precursor,impregnation process,and type of precursor dispersant on the morphology,phase and drug delivery properties were weak.However,when the template to precursor mass ratio was 1:15,the alcohol-water mixed system was used as the dispersant system and calcination temperature was 600?,the morphology,phase and drug delivery properties of ordered porous HA prepared by immersion were better.In addition,compared with nano-HA,drug delivery properties of ordered porous HA were greatly improved.(2)When configuring the precursor solution,it was doped different amounts of Zn and ensured(Ca+Zn)/P?1.6667.Effects of different doped amounts of Zn on the morphology,phase and drug delivery properties of ordered porous HA were investigated.The results showed that when the doping amounts of Zn were increased from 1 mol%to 5 mol%,the morphology of ordered porous HA was not changed obviously.But the phase of ordered porous HA prepared with 1 mol%Zn doped was the best with higher crystallinity,showing the better drug loading and ability of drug release control.Compared with undoped materials,the morphology and phase of ordered porous HA prepared with 1 mol%Zn doped were changed small,but the drug delivery properties were improved significantly,showing the better ability of drug loading and longer drug release time.(3)When doped with different amounts of Mg and based on ensuring(Ca+Mg)/P?1.6667,effects of different doped amounts of Mg on the morphology,phase and drug delivery properties of ordered porous HA were investigated.The results showed that as the doped amounts of Mg increased from 1 mol%to 5 mol%,the morphology of ordered porous HA was changed small only with few defects increased.However,the phase was changed greatly,and the crystallinity was decreased with the doped amount increasing.When the doped amount exceeded 3 mol%,the(3-TCP phase was appeared and became more obvious with the doped amount increasing.So the morphology,phase and drug delivery properties of ordered porous HA doped with 1 mol%Mg were the best between the materials with different doped amounts of Mg.Compared with undoped materials,the morphology was changed small,but the grains were refined with crystallinity reduced,showing ?-TCP phase.The ability of drug loading was improved,however,the ability of drug release control became weaker.(4)(Ca+Zn+Mg)/P?l.6667 was maintained under different co-doped amounts of Zn/Mg,then effects of different Zn/Mg co-doped amounts on the morphology,phase and drug delivery properties of ordered porous HA were investigated.The results showed that as the amounts of Zn/Mg co-doped increasing from 1 mol%to 5 mol%,the defects in morphology were increased more,the crystallinity began to decrease with obvious phase changed,showing other phases such as ?-TCP.Ordered porous HA with 1 mol%Zn/Mg co-doped showed good morphology,phase and drug delivery properties in different doped amounts.Compared with undoped materials,there were more defects in the morphology,meanwhile,the crystallinity was decreased with grain refined.The ability of drug loading was improved,but it was changed little on the ability of drug release control with or without Zn/Mg co-doped.(5)The morphology,phase and drug delivery properties of ordered porous HA with the best performance in different doped processes were compared and analyzed.The results showed that undoped ordered porous HA was shown better morphology and relatively pure phase.The morphology of doped ordered porous HA was changed,showing defects to varying degrees.At the same time,?-TCP phase was generated,and the crystallinity decreased.1 mol%Zn-HA was shown the best ability of drug loading in ordered porous HA with different doped processes.The drug loading of Mg-doped and Zn/Mg co-doped materials was also greatly improved compared to the undoped materials.Among the drug release control abilities,1 mol%Zn-HA was the best,while 1 mol%Mg-HA was weaker in drug release control.1 mol%Zn/Mg co-doped ordered porous HA was shown a smaller difference in drug release control ability with the undoped ordered porous HA.