Tuning dual-drug release from composite scaffolds for bone regeneration

Abstract

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.