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Metformin enhances insulin's effect and increases cells’ sensitivity to insulin. In this paper, nanocomposite was designed and used in the metformin release system, which was able to release the required drug in a controlled manner. In this research, nanoparticles of zinc oxide (ZnO) were prepared via the sol-gel method. The experimental design central composite response surface method was applied for the optimization of the nanoparticles based on varied variables such as the weight of zinc acetate (gr) (X ₁) and the volume of triethanolamine (ml) (X₂). The particle size of the optimized nanoparticle was reported to be 28 ± 21.27 nm; zeta potential and PdI were 25.54 ± 1.64 mV, 0.168 ± 0.05 respectively. The chitosan polymer was used to improve environmental compatibility and increase drug release control; finally, metformin was loaded on the optimized nanocomposite. Structural properties were analyzed using scanning electron microscopy (SEM) X-Ray Diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and Dynamic Light Scattering (DLS). The SEM images showed that the average nanocomposite size was 40 nm. The results of XRD patterns and SEM images were also consistent with each other and the average particle size was the same. Infrared spectrophotometry showed the presence of chitosan used to coat nanoparticles on their surfaces and confirmed the loading of metformin. An in-vitro metformin release from the nanocomposite was conducted in PBS (pH=7.4) and analyzed by a spectrophotometer at 233 nm. Metformin has a high solubility in water, and since it is difficult to prepare a slow release form of high-solubility drugs, the aim of this study was to design a slow-release formulation of metformin with a suitable profile that could control release without explosive release for up to 120 hours.

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Gastric cancer is one of the most common cancers in the world. Its treatments are costly and can cause severe side effects. As a result, treatments with natural compounds, well-established therapeutics, or combinations of both groups may be effective alternatives. p-Coumaric acid (pCA) and metformin (Met) are among such anticancer treatments. Epithelial-mesenchymal transition (EMT) is a multi-purpose process that plays a critical role in gastric cancer. This process involves a complex network of biological markers participating in gastric cancer initiation and metastasis. Subsequently, the agents downregulating the expression of EMT markers may be potential anti-gastric cancer therapeutics. Because the effects of pCA, Met, and their combination on the expression of EMT markers ZEB1, Snail2, Vimentin, and VEGFA have not been inspected, the present study aimed at assessing these effects. MTT assay determined the cytotoxicity of pCA and Met on the AGS cells for 48 hours. Real-time PCR was used to evaluate the changes in the expression levels of these EMT genes after 48 hours. A combination of pCA and Met downregulated the expression of ZEB1 and Vimentin genes at low, non-cytotoxic concentrations. Therefore, they may be potential candidates for further investigations in fighting against gastric cancer.