Preparation Of Ion-doped Hydroxyapatite And The Study Of Its Drug Adsorption Based On Experiment And Molecular Dynamics Simulation

Hydroxyapatite（HAp）is the main inorganic component of human and animal bones,which has good biocompatibility and bioactivity,and is widely used in various fields.Synthetic HAp has certain differences from natural HAp.It has poor corrosion resistance,mechanical properties and stability under acidic conditions.Surface modification,ion doping and other methods can make it have better performance and further improve the universality of application.In this paper,HAp with different morphologies was prepared by hydrothermal method,and HAp was doped with different ions and coated with polydopamine.Based on experiment and theoretical calculation,HAp as doxorubicin（DOX）drug carrier was studied in detail and comprehensively.The morphology,phase composition and specific surface area of the samples were characterized and tested by scanning electron microscopy（SEM）,transmission electron microscopy（TEM）,X-ray diffraction（XRD）,Fourier transform infrared spectroscopy（FTIR）,and specific surface area tester（BET）.Meanwhile,based on first-principles and molecular dynamics simulation,the effects of different ion doping on the lattice parameters and drug loading performance of HAp were investigated,and the simulation calculation provided the theoretical basis for experimental design and analysis of experimental results.Nano-HAp（nHAp）doped with different ions(Zn²⁺,Mg²⁺,Cu²⁺,Fe²⁺,Ba²⁺,F^-)was successfully prepared by hydrothermal method with Ca（NO₃）₂·4H₂O as calcium source,（NH₄）₂HPO₄ as phosphorus source and urea as homogeneous precipitant.nHAp shows a short rod-like structure,and the doping of ions don’t significantly change its morphology and phase composition.The specific surface area of nHAp and its DOX loading efficiency can be significantly improved through ion doping.Among all the samples,Zn-nHAp has a higher specific surface area（101.86 m~2/g）,while the Ba/F-nHAp sample（with a specific surface area of 77.08 m~2/g）shows the highest DOX drug loading of 96.28%.All samples show good slow release behavior of DOX,and the acidic environment is more favorable for drug release.The cumulative release amount of Ba-nHAp is the highest at the same release time.The molecular dynamics simulation results show that the binding between DOX and different samples is mainly achieved by the Ca-O bond formed between oxygen atoms in DOX molecules and Ca²⁺on the sample surface,while more adsorption sites are formed between Ba-nHAp,Ba/F-nHAp and DOX with higher binding energy and thus higher drug loading efficiency,which is consistent with the experimental results.Therefore,the drug loading of the samples not only depends on the specific surface area,but also closely relates to its pore structure,adsorption sites between drug and sample,binding energy and other factors.HAp hollow microspheres doped with different ions(Cu²⁺,F^-)were successfully prepared by hydrothermal method using polyaspartic acid（PASP）as chelating agent.The HAp hollow microspheres have a uniform size of 2-4μm and a large specific surface area.Moreover,ion doping does not change the size and morphology of HAp hollow microspheres.When the concentration of dopamine is 2 g/L,uniform and complete coating can be achieved on the surface of the microspheres,so as to obtain polydopamine（PDA）coated HAp hollow microspheres.Although the specific surface area of the coated samples decreases significantly after PDA coating,the coated samples still have high drug loading efficiency.1Cu/1F-HAp-PDA samples show drug（DOX）loading efficiency up to 91.2%and exhibit excellent photothermal conversion performance and photothermal stability.The molecular dynamics simulations show that PDA and HAp formed mutual binding mainly through Ca-O bonding,while DOX is mainly bound to PDA intermolecularly through hydrogen bonding orπ-πstacking interactions.