Hydroxyapatite crystals as a local delivery system for cisplatin: adsorption and release of cisplatin in vitro

Abstract

This study describes the characteristics of the in vitro binding and release of the anti-tumor drug cisplatin by slurries of synthetic hydroxyapatite crystals carried out in aqueous media. The adsorption of cisplatin by slurries of hydroxyapatite and its release were found to depend significantly on the ionic composition of the aqueous media used. At a constant p H of 7.4, significantly more cisplatin is adsorbed by the hydroxyapatite crystals in the slurry from a chloride-free phosphate buffered solution or a Tris buffered solution than from a buffered phosphate solution containing chloride ions. The amount of hydroxyapatite-bound cisplatin desorbed into solution was also progressively increased as a function of the increasing concentration of chloride in the equilibrating solution. Very little hydroxyapatite-bound cisplatin was released from the crystals in either a Tris or phosphate buffer. These results suggest that it is the hydrated derivatives of cisplatin which are involved in the adsorption of cisplatin by hydroxyapatite crystals. The adsorption data can be expressed as a Freundlich isotherm from which the association constant can be calculated. The rate of release of cisplatin bound to crystals of hydroxyapatite is relatively slow even at the maximum concentration of chloride ions in the phosphate buffer. Approximately 33% of the total cisplatin bound to the crystals of hydroxyapatite was released after 4.35 days. An additional l5'% of the remaining cisplatin bound to the hydroxyapatite cyrstals was released after an additional equilibration with fresh buffer for two weeks (58% of the total cisplatin originally bound). These findings suggest that cisplatin bound to slurries of hydroxyapatite crystals may be useful in the local treatment of malignant tumors.

Interactions of cisplatin with calcium phosphate nanoparticles: In vitro controlled adsorption and release

“…As pointed out by Barroug and Glimcher [3], in this type of solid within a solid formulation, the passage of the drug from the solid CaP device into the surrounding tissue is a complex function of solubilization of the drug, adsorption to the CaP device, and diffusional gradients. In our particulate formation with adsorbed species of cisplatin, drug release is accomplished simply by physiologically present chloride ions upon introduction to the tumor environment [3]. The chloride ions reverse the hydrolysis and acid dissociation of cisplatin to the aquated species that was necessary to induce binding to the CaP [3].…”

“…In our particulate formation with adsorbed species of cisplatin, drug release is accomplished simply by physiologically present chloride ions upon introduction to the tumor environment [3]. The chloride ions reverse the hydrolysis and acid dissociation of cisplatin to the aquated species that was necessary to induce binding to the CaP [3]. Previous research has shown that the chemical and physical characteristics of the apatite crystals, including the chemical composition, structure, porosity, particle size and surface area, as well as the ionic composition of the equilibrating solution (pH, ionic strength, concentration of ion constituents), all play an important role in both the binding and release of the specific chemical components from CaP [3][4][5]9,11].…”

“…The chloride ions reverse the hydrolysis and acid dissociation of cisplatin to the aquated species that was necessary to induce binding to the CaP [3]. Previous research has shown that the chemical and physical characteristics of the apatite crystals, including the chemical composition, structure, porosity, particle size and surface area, as well as the ionic composition of the equilibrating solution (pH, ionic strength, concentration of ion constituents), all play an important role in both the binding and release of the specific chemical components from CaP [3][4][5]9,11]. This sensitivity provides an ideal platform for a controlled drug release vehicle; therefore we have chosen to study the binding and release of cisplatin from apatite.…”

Controlled adsorption and release onto calcium phosphates materials and drug delivery applications

“…. ), by double decomposition according to methods described previously [4,5]. The precipitates were removed by filtration, washed with de-ionized water and lyophilized overnight.…”

Effect of Tryptophan Residues on Adsorption of a Cationic Arginine Rich Polypeptide by Hydroxyapatite Nanoparticles and Following Translocation of the Polypeptide Through a Lipid Vesicle Membrane

“…HAp also has been investigated as a material for drug delivery systems due to its chemical similarity to the inorganic phase of bones as well as its ability to adsorb and release several molecules of biological interest [4][5][6][7][8] .…”