title: Tetracycline-loaded biomimetic apatite: an adsorption study.
abstract: Biomimetic apatites are appealing compounds for the elaboration of bioactive bone-repair scaffolds due to their intrinsic similarity to bone mineral. Bone surgeries are however often heavy procedures, and the infiltration of pathogens may not be totally avoided. To prevent their development, systemic antibiotic prophylaxis is widespread but does not specifically target surgical sites and involves doses not always optimized. A relevant alternative is a preliminary functionalization by an infection-fighting agent. In this work, we investigated from a physicochemical viewpoint the association of a wide-spectrum antibiotic, tetracycline (TC), and a biomimetic nanocrystalline apatite previously characterized. TC adsorption kinetics and isotherm were thoroughly explored. Kinetic data were fitted to various models (pseudo-first-order, pseudo-second-order, general kinetic model of order n, Elovich, double-exponential, and purely diffusive models). The best fit was found for a double-exponential kinetic model or with a decimal reaction order of 1.4, highlighting a complex process with such TC molecules which do not expose high-affinity end groups for the surface of apatite. The adsorption isotherm was perfectly fitted to the Sips (Langmuir-Freundlich) model, while other models failed to describe it, and the Sips exponent greater than unity (1.08) suggested a joint impact of surface heterogeneity and positive cooperativity between adsorbed molecules. Finally, preliminary insights on TC release from pelletized nanocrystalline apatite, in aqueous medium and neutral pH, were obtained using a recirculation cell, indicating a release profile mainly following a Higuchi-like diffusion-limited rate. This work is intended to shed more light on the interaction between polar molecules not exhibiting high-affinity end groups and biomimetic apatites and is a starting point in view of the elaboration of biomimetic apatite-based bone scaffolds functionalized with polar organic drugs for a local delivery.
authors.affiliation: CIRIMAT Carnot Institute, UMR CNRS/INPT/UPS 5085, Faculté des Sciences Pharmaceutiques, University of Toulouse , 35 Chemin des Maraîchers, 31400 Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Cazalbou
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Bertrand
authors.forename: Christophe
authors.initials: C
authors.lastname: Drouet
mesh_terms: D000327:Adsorption; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001031:Apatites / Q000737:chemistry*; D051940:B7-2 Antigen / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry*; D018786:Bone Substitutes / Q000737:chemistry*; D005260:Female; D007700:Kinetics; D008297:Male; D008956:Models, Chemical; D015394:Molecular Structure; D017208:Rats, Wistar; D013752:Tetracycline / Q000737:chemistry*; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D001031:Apatites; D051940:B7-2 Antigen; D018786:Bone Substitutes; C497964:CD86 protein, human; D014867:Water; D013752:Tetracycline