title: Development and dissolution studies of bisphosphonate (clodronate)-containing hydroxyapatite-polylactic acid biocomposites for slow drug delivery.
abstract: An increase in clinical demand on the controlled release of bisphosphonates (BPs) due to complications associated with systemic administration, has been the current driving force on the development of BP drug-release systems. Bisphosphonates have the ability to bind to divalent metal ions, such as Ca2+, in bone mineral and prevent bone resorption by influencing the apoptosis of osteoclasts. Localized delivery using biodegradable materials, such as polylactic acid (PLA) and hydroxyapatite (HAp), which are ideal in this approach, have been used in this study to investigate the dissolution of clodronate (non-nitrogen-containing bisphosphonate) in a new release system. The effects of coral structure-derived HAp and the release kinetics of the composites were evaluated. The release kinetics of clodronate from PLA-BP and PLA-HAp-BP systems seemed to follow the power law model described by Korsmeyer-Peppas. Drug release was quantified by31P-NMR with detection and quantification limits of 9.2 and 30.7 mM, respectively. The results suggest that these biocomposite systems could be tuned to release clodronate for both relatively short and prolonged period of time. In addition to drug delivery, the degradation of HAp supplies both Ca2+and phosphate ions that can help in bone mineralization. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: School of Chemistry and Forensic Science, University of Technology, Sydney, NSW, Australia.
authors.forename: Innocent J
authors.initials: IJ
authors.lastname: Macha
authors.affiliation: CIRIMAT Carnot Institute, CNRS-INPT-UPS, Faculty of Pharmacie, University of Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Cazalbou
authors.affiliation: School of Chemistry and Forensic Science, University of Technology, Sydney, NSW, Australia.
authors.forename: Ronald
authors.initials: R
authors.lastname: Shimmon
authors.affiliation: School of Chemistry and Forensic Science, University of Technology, Sydney, NSW, Australia.
authors.forename: Besim
authors.initials: B
authors.lastname: Ben-Nissan
authors.affiliation: Faculty of Science, University of Technology, Sydney, NSW, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Milthorpe
mesh_terms: D004002:Clodronic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D017886:Durapatite / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D016062:Porosity
chemical_list: D003692:Delayed-Action Preparations; D011091:Polyesters; D004002:Clodronic Acid; C033616:poly(lactide); D017886:Durapatite
keywords: 31P-NMR; coral; drug release; hydroxyapatite; quantification; thin film composites