Porous microspheres of magnesium whitlockite and amorphous calcium magnesium phosphate: microwave-assisted rapid synthesis using creatine phosphate, and application in drug delivery

Abstract

Magnesium whitlockite (WH: Ca₁₈Mg₂(HPO₄)₂(PO₄)₁₂), as an abundant and biologically important biomineral in living bone, is unfortunately difficult to synthesize. Herein, we report a microwave-assisted rapid synthesis of single-phase WH hollow porous microspheres and highly stable amorphous calcium magnesium phosphate (ACMP) porous microspheres by using creatine phosphate (CP) biomolecules as a biocompatible organic phosphorus source. The crystal phase and morphology of the product can be adjusted by the Ca/Mg molar ratio in the initial reaction solution, and CP biomolecules play an important role in the synthesis of the product. The as-synthesized WH hollow porous microspheres and ACMP porous microspheres have high biocompatibility and excellent ability to promote the adhesion and spreading of MC-3T3 osteoblasts. Moreover, WH hollow porous microspheres and ACMP porous microspheres are efficient at the loading and release of the anticancer drug doxorubicin, and exhibit slow, sustainable and pH-responsive drug release behavior. The high drug loading capacity (753 mg g⁻¹) and drug encapsulation efficiency (more than 94%) render the ACMP porous microspheres an appealing carrier for anticancer drug delivery to enhance long-term chemotherapeutic efficacy.