A combined experimental and molecular dynamics simulation study on doxorubicin adsorption on strontium-substituted hydroxyapatite hollow microspheres

Highlights: • Sr-HAp hollow microspheres with 3D hierarchical structure were prepared by a simple hydrothermal method. • The Sr-HAp microspheres have low crystallinity and exhibit remarkable high surface area. • The Sr-HAp microspheres show high DOX loading efficiency and excellent biocompatibility. • The electrostatic interaction between surface Ca ions and carbonyl-O contributes most to the adsorption. Hydroxyapatite (HAp) materials with the functions of bone reconstruction as well as drug release have important applications in treatment of bone diseases. However, it still remains a challenge to synthesize ion-doped HAp with low crystallinity and high surface area to improve its biological responses and drug loading capacity. Herein, strontium-substituted hydroxyapatite (Sr-HAp) hollow microspheres that exhibit high drug loading efficiency and excellent biocompatibility are reported via a simple one-step hydrothermal method. The specific surface area of the as-prepared Sr-HAp microspheres can be as high as 214.69 m²/g. The simulation results show that there is no significant difference in the total binding energy between doxorubicin (DOX) and HAp as well as Sr-HAp. Both HAp and Sr-HAp show high DOX loading efficiency and sustained DOX release behavior. The binding between DOX and Sr-HAp is mainly through the electrostatic interaction between Ca or Sr ions on Sr-HAp surfaces and carbonyl-O or hydroxyl-O in DOX molecule. The findings provide insights into the design and development of drugs used in drug delivery system of HAp or ion-doped HAp materials.