Biomimetic Hydroxyapatite–Drug Nanocrystals as Potential Bone Substitutes with Antitumor Drug Delivery Properties

Abstract

This Full Paper investigates the adsorption and desorption of the anticancer drugs cis‐diamminedichloroplatinum(II) (CDDP, cisplatin) and the new platinum(II) complex di(ethylenediamineplatinum)medronate (DPM), as well as the clinically relevant bisphosphonate alendronate, towards two biomimetic synthetic HA nanocrystalline materials with either plate‐shaped (HAps) or needle‐shaped (HAns) morphologies and different chemico‐physical properties. The adsorption and desorption kinetics are dependent on the specific properties of the drugs and the morphology of the HA nanoparticles. Adsorption of the platinum complexes occurs with retention of the nitrogen ligands but the chloride ligands of cisplatin are displaced. Despite their opposite charges, the negatively charged alendronate bisphosphonate and the positively charged aquated cisplatin are strongly adsorbed, while the neutral DPM complex shows lower affinity towards the negatively charged apatitic surface. The data suggest that adsorption of the two platinum complexes is driven by electrostatic attractions, while interaction between the alendronate and the HA surface takes place by ligand exchange in which the two phosphonate groups of the drug molecule replace two surface phosphate groups. Significantly, adsorption of positively charged hydrolysis species of cisplatin is more favored on the phosphate‐rich HAns surface while adsorption of negatively charged alendronate is more favored on the calcium‐rich HAps surface. The latter type of short‐range electrostatic interactions also appear to dominate the desorption kinetics; consequently, drug release is greater for neutral DPM than for charged alendronate and aquated cisplatin. Moreover, while the release per unit area of charged species is the same for the two types of HAs, the release of DPM is faster from HAns, which is lower in surface calcium, than for HAps. Overall, this work demonstrates that the properties of HA nanocrystals can be modulated in such a way to produce HA/biomolecule conjugates tailored for specific therapeutic applications.

Ab initio modelling of protein–biomaterial interactions: influence of amino acid polar side chains on adsorption at hydroxyapatite surfaces

“…different amino acids (AAs), peptides and proteins may inhibit the HA growth to a different degree. Additionally, calcium phosphate-based nanoparticles have been proposed as suitable materials for loading and securing different drugs, to be delivered afterwards in a controlled way inside a living body [12,13].…”

Evolving application of biomimetic nanostructured hydroxyapatite

“…The adsorption and release of cisplatin, alendronate, and di(ethylenediamineplatinum) medronate have been investigated using two biomimetic synthetic hydroxyapatite nanocrystal materials with either plate-shaped or needle-shaped morphologies and with different physical and chemical surface properties. 167 These bioactive molecules were chosen in order to compare the behavior of metal-based drugs to that of a classical organic drug (alendronate), evaluating the effect of the overall charge of the drug molecule in influencing the drug affinity for apatite nanocrystals with variable structural and chemical properties. The HA surface area and surface charge (Ca/P ratio), as well as the charge on the adsorbed molecules and their mode of interaction with the HA surface, influence the adsorption and release kinetics of the three drugs investigated.…”

The Biomimetic Approach to Design Apatites for Nanobiotechnological Applications

“…The adsorption and release of bioactive molecules are strongly affected not only by the chemical properties of the drug molecule, but also by the chemical and structural characteristics of the HA substrates. The adsorption and release of cisplatin, alendronate and di(ethylendiamineplatinum)medronate have been investigated using two biomimetic synthetic HA nanocrystal materials with either plate-shaped or needle-shaped morphologies and with different physical-chemical surface properties by Palazzo et al (Palazzo et al, 2007). These bioactive molecules were chosen in order to compare the behaviour of metal based drugs to that of a classical organic drug (alendronate), evaluating the effect of the drug molecule overall charge in influencing the drug affinity for apatite nanocrystals with variable structural and chemical different properties.…”