Synthesis, drug-loading performance and molecular dynamics simulation of hydroxyapatite multiphase composite microspheres

To address the limitations of hydroxyapatite (HA) microspheres, such as insufficient drug-loading capacity and severe aggregation, high-performance drug-loaded microspheres via compounding functional materials were prepared and the underlying synergistic enhancement mechanisms were explored. In this study, HA was combined with graphene oxide (GO), gelatin (Gel), and β-cyclodextrin (β-CD) to fabricate a series of drug-loaded composite microspheres, including HA-Gel, HA-GO-Gel, HA-GO-β-CD, HA-GO-β-CD-Gel, using hydrothermal and emulsion crosslinking methods. After loading with curcumin (Cur) drug, the characterization and test results showed that the drug-loading performance of ternary and quaternary composite microspheres was significantly enhanced by introducing β-CD and GO into the HA-Gel binary composite system. Among them, the HA-GO-β-CD-Gel quaternary composite microspheres exhibited more uniform particle size and better dispersion. The encapsulation efficiency and drug loading capacity reached (40.46±1.41)% and (5.58±0.69)%, respectively, with microsphere particle size ranging from 6.9 to 17.4 μm. Molecular dynamics (MD) simulations were further conducted to elucidate the mechanism underlying the enhanced drug-loading performance. Taking the HA-β-CD binary composite microsphere as an example, the results indicated that the adsorption capacity of HA-β-CD composite microspheres for Cur drug molecules was significantly stronger than that of pure HA microspheres, demonstrating improved drug-loading capacity. The simulation results were consistent with the experimental observations. Overall, HA multiphase composite microspheres, particularly the HA-GO-β-CD-Gel quaternary composite microspheres, can effectively improve the drug-loading performance and show promising application potential.