Several diseases, including atherosclerosis, are characterized by inflammation, which is initiated by leukocyte migration to the inflamed lesion. Hence, genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis. Algal-derived polysaccharides are one of the most promising sources for pharmaceutical application, although their mechanism of action is still poorly understood. The present study uses a computational method to anticipate the effect of fucoidan and alginate on interactions with adhesion molecules and chemokine, followed by an assessment of the cytotoxicity of the best-predicted bioactive compound for human monocytic THP-1 macrophages by lactate dehydrogenase and crystal violet assay. Moreover, an in vitro pharmacodynamics evaluation was performed. Molecular docking results indicate that fucoidan has a greater affinity for L-and E-selectin, monocyte chemoattractant protein 1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) as compared to alginate. Interestingly, there was no fucoidan cytotoxicity on THP-1 macrophages, even at 200 µg/mL for 24 h. The strong interaction between fucoidan and L-selectin in silico explained its ability to inhibit the THP-1 monocytes migration in vitro. MCP-1 and ICAM-1 expression levels in THP-1 macrophages treated with 50 µg/mL fucoidan for 24 h, followed by induction by IFN-γ, were shown to be significantly suppressed as eight- and four-fold changes, respectively, relative to cells treated only with IFN-γ. These results indicate that the electrostatic interaction of fucoidan improves its binding affinity to inflammatory markers in silico and reduces their expression in THP-1 cells in vitro, thus making fucoidan a good candidate to prevent inflammation.

Background: The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize drug efficacies. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. Objective: The study aimed to evaluate antitumor activity of the combination therapy of GEM and ATV encapsulated in nanodroplets of microemulsion (ME) formulation in MCF-7 breast cancer cells and healthy HFS human foreskin cells. Method: The physical characterization of drug formulas has been studied by the transmission electron microscope (TEM). The cytotoxicity and efficacy of the formulation were examined by 3(4,5-dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay, light microscopy, and ApopNexin apoptosis detection kit. Results: It has been found that the IC50, inhibitory concentration at which 50 percent of the cells inhibited, for the combination of GEM and ATV at 1:2 ratio, respectively, in the ME (GEM/2ATVME) with a droplet diameter of 4.81±0.86 nm, subjected into the MCF-7 cells for 24h, was similar to the combination of GEM and ATV at 1:1 ratio, respectively, in water (GEM/ATV). According to the FITC/PI assay, 5 µM of GEM/2ATV-ME was less toxic on the HFS cells as higher percentages of viable cells (85.15%) were detected when compared to the GEM/ATV that caused reduction in the percentages of the viable cells (66.45%). Conclusion: Formulating GEM with ATV in ME has improved the therapeutic anticancer potential of both drugs while reducing their side effects on the normal cells.

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.