title: Bone substitute materials delivering zoledronic acid: physicochemical characterization, drug load, and release properties.
abstract: Calcium phosphate-like bone substitute materials have a long history of successful orthopedic applications such as bone void filling and augmentation. Based on the clinical indications, these materials may be loaded with active agents by adsorption offering a perspective for providing innovative drug-delivery systems. The highly effective bisphosphonate zoledronic acid (ZOL) demonstrated a strong affinity to biominerals and is known to significantly reduce osteoclastic activity. Support of early bone formation and reduction of bone resorption can be promoted after implantation of bioceramics releasing ZOL. The aim of this study was to develop an easy to handle approach to combine ZOL with bone substitutes by use of a dipping technique. The properties of three different materials were investigated by using a number of physicochemical methods such as light microscopy, scanning electron microscopy (SEM), dynamic vapor sorption (DVS), true density, and surface area measurement to evaluate the feasibility of being potential drug carriers. Besides physicochemical characterization, the bone substitutes were evaluated by their ZOL-loading capacity in a time- and concentration-dependent manner. Additionally, the materials were assessed as release systems in an in vitro study. A controlled ZOL load in a range of 0.04-1.86 µg/mg material and a release of 0.02-0.18 µg/mg within 30 min is demonstrated. The findings support using the investigated bioceramics as carrier systems to release ZOL. Overall, the results create the base for further development of drug-delivery systems with controlled drug loading and prolonged release and need to be further analyzed in an in vivo study.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Germany.
authors.forename: Torben C
authors.initials: TC
authors.lastname: Sörensen
authors.forename: Jörg
authors.initials: J
authors.lastname: Arnoldi
authors.forename: Philip
authors.initials: P
authors.lastname: Procter
authors.forename: Bernd
authors.initials: B
authors.lastname: Robioneck
authors.forename: Hartwig
authors.initials: H
authors.lastname: Steckel
mesh_terms: D000327:Adsorption; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001861:Bone Regeneration / Q000187:drug effects; D018786:Bone Substitutes / Q000737:chemistry*; D002130:Calcium Phosphates / Q000737:chemistry; D004164:Diphosphonates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D013499:Surface Properties; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D018786:Bone Substitutes; D002130:Calcium Phosphates; D004164:Diphosphonates; D004337:Drug Carriers; D007093:Imidazoles; D000077211:Zoledronic Acid