Direct intercalation of cisplatin into zirconium phosphate nanoplatelets for potential cancer nanotherapy.

We report the use of zirconium phosphate (ZrP) nanoplatelets for the encapsulation of the anticancer drug cisplatin and its delivery to tumor cells. Cisplatin was intercalated into ZrP by direct ion exchange and was tested in vitro for cytotoxicity in the human breast cancer (MCF-7) cell line. The structural characterization of the intercalated cisplatin in ZrP suggests that during the intercalation process, the chloride ligands of the cisplatin complex were substituted by phosphate groups within the layers. Consequently, a new phosphate phase with the platinum complex directly bound to ZrP (cisPt@ZrP) is produced with an interlayer distance of 9.3 Å. The in vitro release profile of the intercalated drug upon a pH stimulus shows that at low pH under lysosomal conditions the platinum complex is released with simultaneous hydrolysis of the zirconium phosphate material, while at higher pH the complex is not released. Experiments with the MCF-7 cell line show that cisPt@ZrP reduced the cell viability up to 40%. The cisPt@ZrP intercalation product is envisioned as a future nanotherapy agent against cancer. Taking advantage of the shape and sizes of the ZrP particles and controlled release of the drug at low pH, it is intended to exploit the enhanced permeability and retention effect of tumors, as well as their intrinsic acidity, for the destruction of malignant cells.

Nanoencapsulation of insulin into zirconium phosphate for oral delivery applications.

The encapsulation of insulin into different kinds of materials for noninvasive delivery is an important field of study because of the many drawbacks of painful needle and syringe delivery such as physiological stress, infection, and local hypertrophy, among others (Khafagy, E.-S.; et al. Adv. Drug Delivery Rev. 2007, 59 (15), 1521-1546). A stable, robust, nontoxic, and viable noninvasive carrier for insulin delivery is needed. We present a new approach for protein nanoencapsulation using layered zirconium phosphate (ZrP) nanoparticles produced without any preintercalator present. The use of ZrP without preintercalators produces a highly pure material, without any kinds of contaminants, such as the preintercalator, which can be noxious. Cytotoxicity cell viability in vitro experiments for the ZrP nanoparticles show that ZrP is not toxic, or harmful, in a biological environment, as previously reported for rats (Zhu, Z. Y.; et al. Mater. Sci. Forum 2009, 620-622, 307-310). Contrary to previous preintercalator-based methods, we show that insulin can be nanoencapsulated in ZrP if a highly hydrate phase of ZrP with an interlayer distance of 10.3 Å (10.3 Å-ZrP or θ-ZrP) is used as a precursor. The intercalation of insulin into ZrP produced a new insulin-intercalated ZrP phase with about a 27 A interlayer distance, as determined by X-ray powder diffraction, demonstrating a successful nanoencapsulation of the hormone. The in vitro release profile of the hormone after the intercalation was determined and circular dichroism was used to study the hormone stability upon intercalation and release. The insulin remains stable in the layered material, at room temperature, for a considerable amount of time, improving the shell life of the peptidic hormone. This type of material represents a strong candidate to developing a noninvasive insulin carrier for the treatment of diabetes mellitus.