The intercalations of insulin and cisplatin into α-zirconium phosphate, using &thetas;-zirconium phosphate as precursor, has been investigated for their future use in drug delivery applications. In addition, the inorganic complexes tris(1,10-phenanthroline)iron(II), tris(2,2’-bipyridine)iron(II), bis(2,2';6',2"-terpyridine)iron(II), and the bidentate ligands 1,10-phenantroline and 2,2’bipyridine have been also intercalated into α-zirconium phosphate, using &thetas;-zirconium phosphate as precursor, with the purpose of elucidating the intercalation mechanism involved in the use of &thetas;-ZrP as precursor. The structural and spectroscopic properties of these materials were investigated.
The first direct intercalation of a protein (the peptidic hormone insulin) into ZrP was accomplished using &thetas;-ZrP as a precursor. The intercalation of insulin into ZrP produced a new insulin-intercalated ZrP phase with a ca. 27 Å interlayer distance, as determined by X-ray powder diffraction, demonstrating a successful nanoencapsulation of the peptidic hormone. The in vitro release profile of the hormone after the intercalation by pH stimulus was determined. The release profile shows a direct dependency with the pH of the medium for the release of the hormone where at low pH the hormone remains in the layered material and at higher pH the insulin is released. Circular dichroism and FTIR spectroscopies were used to study the hormone stability upon intercalation. The insulin remains stable in the layered material, at room temperature, for a considerable amount of time, improving the shelf life of the peptidic hormone. This type of materials represents a strong candidate to develop a non-invasive insulin carrier for the treatment of diabetes mellitus.
Cisplatin, a Pt(II) square planar complex used as an anticancer drug, was also intercalated into zirconium phosphate by direct ion exchange, using &thetas;-ZrP as a precursor. The X-ray powder diffraction patterns show the formation of a new phase with an interlayer distance of ca. 9.3 Å. Based on molecular modeling and spectroscopy data we conclude that this phase corresponds to cisplatin directly bound to the phosphates layers, where cisplatin lost its chloride ligands and the phosphates of the interlayer region coordinate to the Pt(II) complex. The in vitro release profile of the Pt(II) complex after the intercalation by pH stimulus was determined. The release profile shows also a direct dependency with the pH of the medium for the release of the complex, where at low pH the cisplatin is released from the layers and at higher pH the complex remains in the interlayer region.
In order to understand the intercalation mechanism of &thetas;-ZrP, various iron(II) diimines complexes where intercalated, as well as their corresponding bidentate ligands. The intercalation of these species demonstrates that at low loading levels the intercalated molecules are under high hindrance until finally they can overcome the intercalation energy barrier breaking the layer-tolayer interaction. In the initial steps of the intercalation process part of the intercalated species were dissociated in the interlayer region due to the pressure of the layers collapsing over them. The intercalation of the ligand shows a step-by-step intercalation process where first the ligands enter in the interlayer region, reacting with the protons of the interlayer phosphates and forming the protonated species, followed by the accommodation of the ligands in the interlayer region to the maximize their π-π stacking interaction and minimized their electrostatic repulsions.