Reaction of Zoledronate with β-Tricalcium Phosphate for the Design of Potential Drug Device Combined Systems

Abstract

The reaction of aqueous Zoledronate solutions with β-tricalcium phosphate resulted in the precipitation of a crystalline Zoledronate complex on the surface of the calcium phosphate. This complex (CaNa[(HO)(C4H5N2)C(PO3)(PO3H)]·xH2O) was found to be metastable, leading to a pure calcium complex [Ca3[(HO)(C4H5N2)C(PO3)(PO3H)]2·xH2O] upon washing with water. This latter compound was found to release the bisphosphonate in phosphate buffers, in direct proportion to the phosphate concentration, while using a specific in vitro bone resorption model, an inhibition of osteoclastic activity was observed with this material. This suggested that when this composite is implanted in bone tissues, the drug will be released in greater concentration the more the bone is being resorbed, resulting in a decrease of osteoclast activity and making this drug device combination suitable for practical application as a bisphosphonate local delivery system. In addition, the chemical environment of the bisphosphonate moiety in the two reported bisphosphonate/calcium phosphate composites was probed using 31P and 23Na magic-angle-spinning NMR and two-dimensional 31P homonuclear and 31P−1H heteronuclear correlation experiments, thus giving clear evidence that modern high-resolution solid-state NMR is a powerful tool for the characterization of calcium phosphate-based biomaterials.

Bisphosphonate-Based Strategies for Bone Tissue Engineering and Orthopedic Implants

“…Most commonly, the linkage of the drug to inorganic materials is made by soaking the inorganic scaffold in a BP solution, and recent examples of this method have been published in the last few years. 32,34,36,37,40,[132][133][134][135] In a relevant study, Boanini et al (2008) 132 synthesized HA nanocrystals loaded with different ALN contents (3.9, 6.2, 7.1 wt%). The in vitro evaluation showed that the presence of the BP in the composite nanocrystals produced a reduction in the number of osteoclasts of approximately 30% and an increase in osteoblastic growth and differentiation.…”

“…During the last decade, several studies that are related to the development of delivery systems for the controlled release of BP have been published. 7,29,[31][32][33][34][35][36][37][38][39][40][41] Smart methods of local drug delivery systems could increase the drug activity and specificity by concentrating the release of BP to bone sites and could reduce side effects at extra-skeletal sites. For those interested in further reading, a recent review summarizes the latest advances in the application of BPs for in situ orthopedic medication and treatments.…”

DNA adsorbed on hydroxyapatite surfaces

“…6 This similarity motivated the application of HAp as a synthetic biomaterial as has been evidenced in a large number of studies. [7][8][9][10][11][12][13][14][15] Furthermore, the formation of HAp can be regulated by DNA, which acts as a template in the process of "biomineralization". [16][17][18][19] This phenomenon is particularly important for biomedical applications requiring the protection of such biomolecules from aggressive environmental conditions.…”

β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

“…Different types of CaP ceramics, such as hydroxyapatite (HA) [4], beta-tricalcium phosphate (β-TCP) [5], biphasic calcium phosphate (BCP) [6], amorphous calcium phosphate (ACP) [7] and calcium-deficient HA (CDHA) [8], have been studied as drug carriers in orthopaedic DDS applications. Among the different compositions of CaP materials, beta-tricalcium phosphate (β-TCP-Ca 3 (PO 4 ) 2 ) has attracted attention owing to its bioresorbability, which permits a gradual replacement of the implant by the newly formed bone [1,9].…”

“…In the mentioned examples [10][11][12][13][14], the feasibility of β-TCP as a potential drug carrier has been proved, its drug release behaviour in vitro and/or in vivo has been shown and the effect of parameters such as carrier porosity or chemical composition of β-TCP on drug delivery has been discussed. However, the type of interaction between the drug and the β-TCP drug carrier, which is an important factor in controlling drug release kinetics, has been highlighted in only a few studies [5,15].…”