Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity-drug interaction

In 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, owing to its role as a nucleating agent of hydroxyapatite and to a drying effect on the paste. Doxycycline-loaded CPFs presented interconnected macroporosity, which increased drug availability compared with calcium phosphate cements, and was a critical parameter controlling the release kinetics which followed a non-Fickian diffusion model. Up to 55% (1mg) of the drug was released progressively in 5days, 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 enables tuning of the local delivery of drugs from injectable calcium phosphates.