BMB-8 Nanoparticle Uptake in Human Intestinal Epithelial Cells
Abstract
Inflammatory bowel disease (IBD) is a class of autoimmune diseases of unknown cause that includes Crohn’s disease and ulcerative colitis. While only palliative therapies are available, patients with IBD struggle with diarrhea, abdominal pain, and other chronic symptoms. This study is interested in investigating the multidrug resistance gene (MDR) which encodes for the small molecule pump P-glycoprotein (P-gp). This protein is responsible for regulating and controlling drug absorption and can be found in various parts of the body including the epithelial cells of the intestines. Polymorphisms of the MDR1 gene (encoding P-gp) have been linked directly to IBD in humans. A novel mechanism of drug delivery is through silicone oxide (SiO2) nanoparticles, potentially increasing drub absorption by IBD patients. The goal of this study is to characterize the ability of MDR deficient (MDR-/-) intestinal cells to uptake nanoparticles for possible drug delivery applications. To test this, control and MDR-/- Caco-2 intestinal cells were incubated for 4, 8, 12, or 24 hours with fluorescently labeled nanoparticles. Nanoparticle uptake was measured via flow cytometry and fluorescent microscopy. The MDR-/- Caco-2 cells showed an overall lower percentage of nanoparticle positive cells than control cells with a significant difference in the 4- and 8- hour incubation time points. The MDR-/- Caco-2 cells showed an overall lower mean fluorescence intensity (MFI) of the nanoparticles than the control cells with a significant difference in the 8- and 12-hour incubation time points. Imaging of the cells containing the nanoparticles showed fewer MDR-/- cells containing nanoparticles, however, those with nanoparticles had a higher concentration of particles. The changes we detected suggest, although the MDR-/- cells are able to uptake nanoparticles, they exhibit less incorporation of the nanoparticles inside the cells which leads us to believe nanoparticles will be a less effective drug delivery method for IBD patients with MDR mutations.
BMB-8 Nanoparticle Uptake in Human Intestinal Epithelial Cells
University Readiness Center Greatroom
Inflammatory bowel disease (IBD) is a class of autoimmune diseases of unknown cause that includes Crohn’s disease and ulcerative colitis. While only palliative therapies are available, patients with IBD struggle with diarrhea, abdominal pain, and other chronic symptoms. This study is interested in investigating the multidrug resistance gene (MDR) which encodes for the small molecule pump P-glycoprotein (P-gp). This protein is responsible for regulating and controlling drug absorption and can be found in various parts of the body including the epithelial cells of the intestines. Polymorphisms of the MDR1 gene (encoding P-gp) have been linked directly to IBD in humans. A novel mechanism of drug delivery is through silicone oxide (SiO2) nanoparticles, potentially increasing drub absorption by IBD patients. The goal of this study is to characterize the ability of MDR deficient (MDR-/-) intestinal cells to uptake nanoparticles for possible drug delivery applications. To test this, control and MDR-/- Caco-2 intestinal cells were incubated for 4, 8, 12, or 24 hours with fluorescently labeled nanoparticles. Nanoparticle uptake was measured via flow cytometry and fluorescent microscopy. The MDR-/- Caco-2 cells showed an overall lower percentage of nanoparticle positive cells than control cells with a significant difference in the 4- and 8- hour incubation time points. The MDR-/- Caco-2 cells showed an overall lower mean fluorescence intensity (MFI) of the nanoparticles than the control cells with a significant difference in the 8- and 12-hour incubation time points. Imaging of the cells containing the nanoparticles showed fewer MDR-/- cells containing nanoparticles, however, those with nanoparticles had a higher concentration of particles. The changes we detected suggest, although the MDR-/- cells are able to uptake nanoparticles, they exhibit less incorporation of the nanoparticles inside the cells which leads us to believe nanoparticles will be a less effective drug delivery method for IBD patients with MDR mutations.