Development and dissolution studies of bisphosphonate (clodronate)-containing hydroxyapatite–polylactic acid biocomposites for slow drug delivery Innocent J. Macha 1 , Sophie Cazalbou 2 , Ronald Shimmon 1 , Besim Ben-Nissan 1 * and Bruce Milthorpe 3 1 School of Chemistry and Forensic Science, University of Technology, Sydney, NSW, Australia 2 CIRIMAT Carnot Institute, CNRS–INPT–UPS, Faculty of Pharmacie, University of Toulouse, France 3 Faculty of Science, University of Technology, Sydney, NSW, Australia Abstract An increase in clinical demand on the controlled release of bisphosphonates (BPs) due to complica- tions 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 Ca 2+ , in bone mineral and prevent bone resorption by influencing the apoptosis of osteoclasts. Local- ized 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 by 31 P-NMR with detection and quanti- fication 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 addi- tion to drug delivery, the degradation of HAp supplies both Ca 2+ and phosphate ions that can help in bone mineralization. Copyright © 2015 John Wiley & Sons, Ltd. Received 16 January 2015; Revised 12 May 2015; Accepted 12 June 2015 Keywords drug release; thin film composites; coral; hydroxyapatite; 31 P-NMR; quantification 1. Introduction Bisphosphonates (BPs) have the ability to bind to divalent metal ions in bone mineral and prevent bone resorption by influencing apoptosis in osteoclasts (Weinstein et al., 2009). BPs are characterized by the structure P–C–P, in which germinal bisphosphonates share the same carbon atom; they are analogues of pyrophosphates (P–O–P), in which the central oxygen atom is replaced by a carbon atom, to render them resistant to enzymatic hydrolysis. In addition, two side-groups or chains normally attach to the central carbon atom, resulting in a number of bisphosphonate derivatives with varying potencies in terms of their antiresorptive activity (Shinoda et al., 1983). The clinical uses of bisphosphonates include the prevention and treatment of diseases related to osteoclast-mediated bone resorption, including tumour- associated osteolysis, bone metastasis, primary and sec- ondary hyperparathyroidism and osteoporosis (Kanis et al., 1996). Nitrogen-containing bisphosphonates (NBPs) have been first-choice drugs for the clinical treatment of diseases involving increased bone resorption, because of their greater effect than non-nitrogen-containing bisphosphonates (non-NBPs). It has been reported that NBPs, among many side-effects, might also cause osteonecrosis of the jaw in people with a history of oral and/or maxillofacial surgery, periodontal surgery or end- odontic therapy (Capsoni et al., 2006; Heng et al., 2012; *Correspondence to: Besim Ben-Nissan, PO Box 123, Broadway 2007, NSW, Australia. E-mail: Besim.Ben-Nissan@uts.edu.au Copyright © 2015 John Wiley & Sons, Ltd. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE RESEARCH ARTICLE J Tissue Eng Regen Med (2015) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/term.2066