In situ fabrication of alendronate-loaded calcium phosphate microspheres: Controlled release for inhibition of osteoclastogenesis

Bioabsorbable calcium phosphate (CaP) microspheres that can incorporate alendronate (ALD) through an in situ loading process and can control the ALD release rate have been described. ALD loading into CaP microspheres could be accomplished by emulsification (water-in-oil) and a subsequent CaP nucleation/growth process within the water droplets, which was initiated by a urea-mediated solution precipitation technique. ALD-loaded microspheres with a mean size range of 163–195 μm were obtained in a spherical shape. Inductively coupled plasma mass spectroscopy (ICP-MS), spectrophotometric analysis, and thermogravimetric analysis (TGA) showed that the amount of ALD loaded into the microspheres increased when the ALD feed content increased. Energy-dispersive X-ray spectroscopy (EDX) analysis revealed that the in situ loading process enabled the ALD loading throughout the microspheres. X-Ray diffraction (XRD) analysis demonstrated that crystalline hydroxyapatite (HAp) and amorphous CaP phases coexisted within the microspheres. In addition, the increased loading of ALD resulted in a larger proportion of the amorphous CaP phase within the microspheres. The ALD release rate could be controlled depending on the dissolution rate of microspheres, and ALD could be released over a period of 40 days. The evaluation of the biological activity showed that ALD-loaded CaP microspheres directly blocked osteoclast formation by releasing ALD to monocytic precursor cells and effectively inhibiting their differentiation into osteoclasts.

Graphical abstractWe developed an in situ fabrication approach for alendronate-loaded calcium phosphate (CaP) microspheres through emulsification and a subsequent CaP nucleation/growth process. CaP microspheres released alendronate in a controlled manner and effectively inhibited the osteoclast differentiation.Figure optionsDownload full-size imageDownload as PowerPoint slide