Agustin Diaz - Nanoencapsulation of Insulin into Zirconium Phosphate for Oral Delivery Applications

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      Biomacromolecules Article ASAP


      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 Å 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.

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