title: Drug delivery from injectable calcium phosphate foams by tailoring the macroporosity-drug interaction.
abstract: 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.
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), Av. Diagonal 647, 08028 Barcelona, Spain; Centre for Research in Nanoengineering, Technical University of Catalonia (UPC), C/Pascual i Vila 15, 08028 Barcelona, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Maria de Luna 11, Ed. CEEI, 50118 Zaragoza, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pastorino
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), Av. Diagonal 647, 08028 Barcelona, Spain; Centre for Research in Nanoengineering, Technical University of Catalonia (UPC), C/Pascual i Vila 15, 08028 Barcelona, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Maria de Luna 11, Ed. CEEI, 50118 Zaragoza, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Canal
authors.affiliation: Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), Av. Diagonal 647, 08028 Barcelona, Spain; Centre for Research in Nanoengineering, Technical University of Catalonia (UPC), C/Pascual i Vila 15, 08028 Barcelona, Spain; Biomedical Research Networking Centre in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Maria de Luna 11, Ed. CEEI, 50118 Zaragoza, Spain. Electronic address: maria.pau.ginebra@upc.edu.
authors.forename: Maria-Pau
authors.initials: MP
authors.lastname: Ginebra
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002130:Calcium Phosphates; D004318:Doxycycline / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D016062:Porosity; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002130:Calcium Phosphates; D004337:Drug Carriers; C020243:calcium phosphate; D004318:Doxycycline
keywords: Calcium phosphate cement; Controlled release; Drug delivery; Foam; Scaffold