Interaction between a Bisphosphonate, Tiludronate, and Biomimetic Nanocrystalline Apatites

Abstract

Bisphosphonates (BPs) are well established as successful antiresorptive agents for the prevention and treatment of bone diseases such as osteoporosis and Paget's disease. The aim of this work was to clarify the reaction mechanisms between a BP molecule, tiludronate, and the nanocrystalline apatite surface. The adsorption of tiludronate on well-characterized synthetic biomimetic nanocrystalline apatites with homogeneous but different compositions and surface characteristics was investigated to determine the effect of the nanocrystalline apatite substrate on the adsorption behavior. The results show that the adsorption of tiludronate on nanocrystalline biomimetic apatite surfaces varies over a large range. The most immature apatitic samples exhibited the highest affinity and the greatest amount adsorbed at saturation. Maturation of the nanocrystals induces a decrease of these values. The amount of phosphate ion released per adsorbed BP molecule varied, depending on the nanocrystalline substrate considered. The adsorption mechanism, although associated with a release of phosphate ions, cannot be considered as a simple ion exchange process involving one or two phosphate ions on the surface. A two-step process is proposed consisting of a surface binding of BP groups to calcium ions associated with a proton release inducing the protonation of surface orthophosphate ions and their eventual solubilization.

Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity

“…The presence of alendronate on the crystals after interaction was proven by FT-IR and TGA analysis. The adsorption isotherm fitted well with a Langmuir type isotherm in agreement with the data reported in previous studies [36], suggesting that bisphosphonates are strongly attached to nHA by interactions at the calcium site where the bidentate and tridentate coordination of the P-C-P and -OH domains of the bisphosphonates are known to act [36].…”

“…According to the Langmuir model, the theoretical maximum adsorbed amount of alendronate (Q m ) was 0.43 mg mg -1 and the affinity constant (K L ) was 10.9 ml mg -1 . The obtained value of K L is similar to those generally reported for the other bisphosphonates adsorption[36]. The presence of the adsorption plateau at low equilibrium concentration is an indicator of high affinity of alendronate for the surface of nHA.…”

Adsorption of nucleotides on biomimetic apatite: The case of adenosine 5′ monophosphate (AMP)

“…The chemical composition of the apatite compound synthesized here was determined from titrations by complexometry for the determination of the calcium content, by spectrophotometry for the total phosphate content (determination of the sum of PO 4 3-and HPO 4 2-ions, using the phospho-vanado-molybdenic method [33] and by coulometric method (UIC, Inc. CM 5014 coulometer with CM 5130 acidification unit) for the carbonate content. Thermogravimetric analyses (TG-DTA) were performed for evaluating the amount of hydration water contained in the AMP sodium salt, using a Setaram Instrumentation SETSYS evolution system, with a heating rate of 5°C/min, from 25°C to 900 °C in air.…”

“…In particular, hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , HA) is the basic mineral constituent of enamel microcrystals; in contrast, the mineral part of bone (65-75 wt.%, depending on age and sex) and of dentin is composed of a hydrated nonstoichiometric apatite phase formed of nanosized crystals and exhibiting a low degree of crystallinity [1,2]. Besides biological apatites, various studies have been devoted to the preparation, under close-to-physiological conditions (temperature, pH), of synthetic nanocrystalline apatites analogous to bone mineral [3][4][5]. As in bone, "biomimetic" apatite nanocrystals have the particularity to expose a structured but metastable hydrated surface layer, containing labile ions (e.g.…”

“…As in bone, "biomimetic" apatite nanocrystals have the particularity to expose a structured but metastable hydrated surface layer, containing labile ions (e.g. Ca 2+ , HPO 4 2− , CO 3 2− …) located in "non-apatitic" environments, as evidenced previously [6][7][8][9][10][11][12][13]. These surface ions were also shown to be easily "exchangeable" in solution with ions from the surrounding medium [11,14,15], leading to very peculiar surface properties [16].…”