RESUMO
This work presents the tuning of drug-loaded scaffolds for bone regeneration as dual-drug delivery systems. Two therapeutic substances, zoledronic acid (anti-osteoporotic drug) and ibuprofen (anti-inflammatory drug) were successfully incorporated in a controlled manner into three dimensional designed porous scaffolds of apatite/agarose composite. A high-performance liquid chromatography method was optimized to separate and simultaneously quantify the two drugs released from the dual-drug codelivery system. The multifunctional porous scaffolds fabricated show a very rapid delivery of anti-inflammatory (interesting to reduce inflammation after implantation), whereas the anti-osteoporotic drug showed sustained release behaviour (important to promote bone regeneration). Since ibuprofen release was faster than desired, this drug was encapsulated in chitosan spheres which were then incorporated into the scaffolds, obtaining a release profile suitable for clinical application. The results obtained open the possibility to simultaneously incorporate two or more drugs to an osseous implant in a controlled way improving it for bone healing application.
Assuntos
Regeneração Óssea , Sistemas de Liberação de Medicamentos , Alicerces Teciduais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Apatitas/química , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/química , Carbonatos/química , Quitosana/química , Difosfonatos/administração & dosagem , Difosfonatos/química , Liberação Controlada de Fármacos , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Imidazóis/administração & dosagem , Imidazóis/química , Nanopartículas/química , Sefarose/química , Ácido ZoledrônicoRESUMO
Porous 3-D scaffolds consisting of gelatine and Si-doped hydroxyapatite were fabricated at room temperature by rapid prototyping. Microscopic characterization revealed a highly homogeneous structure, showing the pre-designed porosity (macroporosity) and a lesser in-rod porosity (microporosity). The mechanical properties of such scaffolds are close to those of trabecular bone of the same density. The biological behavior of these hybrid scaffolds is greater than that of pure ceramic scaffolds without gelatine, increasing pre-osteoblastic MC3T3-E1 cell differentiation (matrix mineralization and gene expression). Since the fabrication process of these structures was carried out at mild conditions, an antibiotic (vancomycin) was incorporated in the slurry before the extrusion of the structures. The release profile of this antibiotic was measured in phosphate-buffered saline solution by high-performance liquid chromatography and was adjusted to a first-order release kinetics. Vancomycin released from the material was also shown to inhibit bacterial growth in vitro. The implications of these results for bone tissue engineering applications are discussed.
