Synthesis and characterization of insulin/zirconium phosphate@TiO₂ hybrid composites for enhanced oral insulin delivery applications

Abstract

In this work, a series of composites of insulin (Ins)/zirconium phosphate (ZrP) were synthesized by intercalation method, then, these composites were coated with TiO₂ by sol-gel method to prepare Ins/ZrP@TiO₂ 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 TiO₂ (30, 50, 100 wt %) by using titanium tetra n-butoxide, as precursor. Formation of intercalated Ins/ZrP and Ins/ZrP@TiO₂ hybrid composites was characterized by FT-IR, FE-SEM, BET and XRD analysis. Zeta potential of the optimized Ins/ZrP@TiO₂ hybrid composite was determined −27.2 mV. Cytotoxic effects of the optimized Ins/ZrP@TiO₂ 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 TiO₂ coating enhanced the drug entrapment considerably, and reduced the drug release. The Ins/ZrP composites without TiO₂ coating released the whole drug after 30 min in pH 7.4 (phosphate buffer solution) while the TiO₂-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.

Keywords:

• Zirconium phosphate
• hybrid composite
• porous coating
• drug delivery
• insulin
• intercalation

Acknowledgements

The authors thank the Research Council of Isfahan University of Technology and Center of Excellency in the Chemistry Department of Isfahan University of Technology for supporting of this work.

Disclosure statement

The authors report no conflicts of interest and are responsible for all of the paper contents.