Feedback-controlled release of alendronate from composite microparticles

Extended bone fractures or fractures coexisting with bone disorders can lead to non-unions where surgical intervention is required. Composite drug delivery systems are being used increasingly more in order to treat such defects locally. Alendronate (ALD), a bisphosphonate extensively used in clinical practice to treat conditions, such as osteoporosis, has been shown to assist bone fracture healing through its antiresorptive capacity. This study reports the development of a polymeric composite system for the in situ delivery of ALD, which possesses enhanced encapsulation efficiency (EE%) and demonstrates controlled release over a 70-day period. ALD and calcium phosphate (CaP) were incorporated within poly (lactic-co-glycolic acid) (PLGA) microspheres, giving rise to a 70% increase in EE% compared to a control system. Finally, a preliminary toxicological evaluation demonstrated a positive effect of the system on pre-osteoblastic cells over 72 h.