Target delivery and controlled release of the chemopreventive drug sulindac that possesses low water solubility present a great challenge for its pharmaceutical industry. Here, we offered an advanced nanomatrix formulation system of sulindac based on layered double hydroxide materials. The X-ray analysis and infrared spectroscopy confirmed the incorporation of sulindac into the gallery of the layered double hydroxides. The incorporation ratios of sulindac were recorded to be 45, 31 and 20 for coprecipitation, anion-exchange and reconstruction techniques, respectively. The scanning electron microscopy showed a nanomatrix-structure of ~50 nm. The release studies of sulindac-nanomatrix showed a 96% controlled release at the small intestine solution during 3 h(s), indicating an enhancement in the dissolution profile of sulindac after the matrix formation. The layered structure of the matrix supplied sulindac with a well-ordered structure and a relatively hydrophobic microenvironment that controlled the guest hydrolysis and reactivity during the release process. The laminar structure of layered double hydroxides offered a safe preservation for sulindac against photodecarboxylation, and enhanced the drug thermal stability from 190 to 230° C. The ionic electrostatic interaction of sulindac through its acidic group with layered double hydroxides demolished the gastrointestinal ulceration.
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