Variability of The Drug Response To Nsaids According To Cox-2 Genetic Polymorphism

Abstract

Background: Metformin is a widely used anti-diabetic evaluated by several studies for its anti-cancer properties. However, the role of loaded metformin nanoparticles (NPs) in cancer therapy has not been investigated. This study addresses the cytotoxic effect of metformin and metformin cubosomes on Hct-116 and Caco-2 colorectal cancer (CRC) cell lines. Methods: Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of PluronicF-127 as a stabilizer. The loaded cubosomes were characterized in vitro. Design expert ® software was used for planning and analysis of the experimental trials to select the optimized formulation. Inhibitory effects of metformin cubosomes and the drug alone were investigated by Sulphorhodamine-B (SRB) assay. Results: The particle size, polydispersity index and zeta-potential were determined and revealed nanometer-sized particles with a narrow particle size distribution of 110-160 nm size and cubical morphology. Using the SRB assay, we demonstrate that drug-incorporated NPs induced significant toxicity on CRC cells compared to unloaded cubosomes or the drugs alone. Serial dilutions of empty cubosomes were added to both cell lines to determine their toxicity. Likewise, dilutions of metformin were tested and the concentration that inhibited 50% (IC50) of the cells was determined. The study revealed a decrease in the IC50 of metformin to 20 and 28mM in Caco-2 and Hct-116 cells after its formulation in cubosomes compared to 55 and 50mM of the drug alone respectively. Conclusions: These findings indicate that incorporation of low metformin concentrations in cubosomes profoundly increases its cytotoxic effect on colorectal cancer cells compared to the unformulated drug.