Please cite this article as: Pastorino, D., Canal, C., Ginebra, M-P., Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity-drug interaction, Acta Biomaterialia (2014), doi: http://dx.doi.org/10. 1016/ j.actbio.2014.10.031 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
AbstractIn this work novel injectable Calcium Phosphate Foams (CPFs) were combined with an antibiotic (Doxycycline) to design an innovative dosage form for bone regeneration.The material structure, its drug release profile and antibiotic activity were investigated, while its clinical applicability was assessed through cohesion and injectability tests.Doxycycline had a clear effect on both the micro-and macro-structure of the CPFs due to its role as nucleating agent of hydroxyapatite and a drying effect on the paste. Doxycycline-loaded CPFs presented interconnected macroporosity, which increased drug availability as compared to Calcium Phosphate Cements, and was a critical parameter controlling the release kinetics, which followed a non-Fickian diffusion model. Up to 55% (1 mg) of the drug was released progressively in 5 days, the percentage released being proportional to the macroporosity of the CPFs. All Doxycycline-containing foams had immediate cohesion and were injectable. Moreover, antibacterial activity was observed against Staphylococcus Aureus and Escherichia Coli. Thus, in addition to enhancing osteoconduction and material resorption, macroporosity allows tuning the local delivery of drugs from injectable calcium phosphates.