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The Gradual Release of Alendronate for the Treatment of Critical Bone Defects in Osteoporotic and Control Rats

Purpose: Osteoporosis is a severe health problem with social and economic impacts on society. The standard treatment consists of the systemic administration of drugs such as bisphosphonates, with alendronate (ALN) being one of the most common. Nevertheless, complications of systemic administration occur with this drug. Therefore, it is necessary to develop new strategies, such as local administration.

Methods: In this study, emulsion/dispersion scaffolds based on W/O emulsion of PCL and PF68 with ALN, containing hydroxyapatite (HA) nanoparticles as the dispersion phase were prepared using electrospinning. Scaffolds with different release kinetics were tested in vitro on the co-cultures of osteoblasts and osteoclast-like cells, isolated from adult osteoporotic and control rats. Cell viability, proliferation, ALP, TRAP and CA II activity were examined. A scaffold with a gradual release of ALN was tested in vivo in the bone defects of osteoporotic and control rats.

Results: The release kinetics were dependent on the scaffold composition and the used system of the poloxamers. The ALN was released from the scaffolds for more than 22 days. The behavior of cells cultured in vitro on scaffolds with different release kinetics was comparable. The difference was evident between cell co-cultures isolated from osteoporotic and control animals. The PCL/HA scaffold show slow degradation in vivo and residual scaffold limited new bone formation inside the defects. Nevertheless, the released ALN supported bone formation in the areas surrounding the residual scaffold. Interestingly, a positive effect of systemic administration of ALN was not proved.

Conclusion: The prepared scaffolds enabled tunable control release of ALN. The effect of ALN was proved in vitro and in in vivo study supported peri-implant bone formation.

Comments：

The results of this study suggest that emulsion/dispersion scaffolds based on a W/O emulsion of PCL and PF68 with ALN and containing HA nanoparticles as the dispersion phase can be used to deliver ALN locally in the treatment of osteoporosis. The scaffolds showed a gradual release of ALN over a period of more than 22 days, and the results of cell cultures in vitro and in vivo studies showed a positive effect of ALN on bone formation. The study suggests that local administration of ALN in this form could provide a new strategy for treating osteoporosis and may be a more effective alternative to systemic administration.

Related Products

Cat.No. Product Name Information
S1624 Alendronate sodium trihydrate Alendronate sodium trihydrate (G-704650, MK-217), a nitrogen-containing bisphosphonate, is a potent inhibitor of bone resorption used for the treatment and prevention of osteoporosis.

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