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.