A Study Of Alendronate-loaded Calcium Phosphate Cement

Calcium phosphate cement (CPC), as an injectable bone substitute material is significantin bone defect treatment. Drugs and biological molecules are often incorporated into CPC topromote the healing of bone defects and treat some bone disease, due to its goodbiocompatibility and non-exothermic self-setting property. In this work, alendronate(ALN)-loaded CPC was prepared and the influences of the content of ALN on the settingtime, microstructure of hydrate, porosity, mechanical strength, in vitro drug release,rheological properties and injectability of CPC were systematically investigated. The effectsof different liquid/powder rate (mL/g) on the properties of ALN-loaded CPC have also beeninvestigated, so as to obtain a more suitable liquid/powder rate. In addition, an ALN-loadedCPC microsphere was prepared in this study. The poly(lactic-co-glycolic acid)(PLGA) wasused to package the microsphere for the purpose of reducing the degree of initial burstrelease.The results showed that the addition of ALN had no effect on the final hydration productof CPC, but it affected the setting process and prolonged the setting time. With the incrementof ALN content, the hydroxyapatite crystals of cured CPC became smaller; and the hydratedCPC became more compact with lower porosity, which resulted in the improvement ofcompressive strength of CPC with a drug-loaded amount less than1wt%. The thixotropy ofthe CPC slurry was promoted with increasing the ALN content, which could enhance thestability of the slurry. The injectability was dramatically improved due to the addition of ALN,which was corresponding to the decrease of viscosity and the promotion of slurry stability.During the in vitro drug release, the initial burst release turned up for all formulations and thedegree of burst release was different from each other. The cell experiments showed that CPCwith a drug content less than1.0wt%can promote the osteogenic differentiation of the ratbone marrow mesenchymal stem cells (rBMSCs), while the CPC with high drug contentmight had cytotoxicity. When increasing the liquid/powder rate from0.25mL/g to0.35mL/g,a more watery paste was obtained due to the effect of ALN on the surface property of CPCparticles. This was in favor of the dissolution-precipitation reactions of CPC, so as todecrease its porosity and increase the compressive strength. The ALN-loaded CPC microsphere had a good sphericity and smooth surface, and the2.0wt%ALN-CPCmicrosphere had better compressive strength and excellent property of anti-disintegration.Compared to the CPC block, the initial burst release behavior was more serious in thisdrug-loaded microsphere. But this effect can be effectively controlled by coating PLGA onthe surface of the microsphere.This work would allow advances in understanding the effect of ALN on the settingprocess and physical and chemical properties of CPC; and provide a new strategy for clinicalapplication ofALN-loaded CPC.