Abstract
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.
Highlights
Bone performs a variety of tasks critical to human physiology [1]
Under 7000 rpm homogenization speed, an increase in homogenization time leads to a decrease in the surface-weighted average (SWA) and d50 of the particle distribution
It has been demonstrated that calcium phosphate (CaP) particle preparation parameters affect the size and morphology of the particles and the phase of the mineral ranging from amorphous hydroxyl apatite to brushite and to highly crystalline HA [22]
Summary
Apart from its most commonly acknowledged role as the body’s structural component, bone tissue performs other functions, such as the protection and support of other internal organs, production of blood cells, and storage of mineral salts [2]. In complex cases, damaged or diseased tissue is unable to regenerate, and, in such cases, surgical intervention is required. Research shifted to the development of bone grafts, namely autografts or allografts [1,2,5]. Both types of graft are associated with limited availability, prolonged recovery, donor-site morbidity, and disease transmittance. There is a clinical need to develop a synthetic alternative [8,9]
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