Synthesis and characterization of insulin/zirconium phosphate@TiO hybrid composites for enhanced oral insulin delivery applications.

In this work, a series of composites of insulin (Ins)/zirconium phosphate (ZrP) were synthesized by intercalation method, then, these composites were coated with TiO by sol-gel method to prepare Ins/ZrP@TiO hybrid composites and the drug release of the composites was investigated by using UV-Vis spectroscopy. Ins/ZrP (10, 30, 60 wt%) composites were prepared by intercalation of insulin into the ZrP layers in water. Then Ins/ZrP composites were coated with different amounts of TiO (30, 50, 100 wt %) by using titanium tetra n-butoxide, as precursor. Formation of intercalated Ins/ZrP and Ins/ZrP@TiO hybrid composites was characterized by FT-IR, FE-SEM, BET and XRD analysis. Zeta potential of the optimized Ins/ZrP@TiO hybrid composite was determined -27.2 mV. Cytotoxic effects of the optimized Ins/ZrP@TiO hybrid composite against HeLa and Hek293T cell lines were evaluated using MTT assay and the results showed that designed drug delivery system was not toxic in biological environment. Compared to the Ins/ZrP composites, incorporation of TiO coating enhanced the drug entrapment considerably, and reduced the drug release. The Ins/ZrP composites without TiO coating released the whole drug after 30 min in pH 7.4 (phosphate buffer solution) while the TiO-coated composites released the entrapped drug after 20 h. In addition to increasing the shelf life of hormone, this nanoencapsulation and nanocoating method can convert the insulin utilization from injection to oral and present a painless and more comfortable treatment for diabetics.