The delivery of drugs into solid tumors is not trivial due to obstructions in the tumor microenvironment. Innovative drug delivery vehicles are currently being designed to overcome this challenge. In this research, computational fluid dynamics (CFD) simulations were used to evaluate the behavior of several drug delivery vectors in tumor capillaries—specifically motile bacteria, non-motile bacteria, and nanoparticles. Red blood cells, bacteria, and nanoparticles were imposed in the flow using the immersed boundary method. A human capillary model was developed using a novel method of handling deformable red blood cells (RBC). The capillary model was validated with experimental data from the literature. A stochastic model of bacteria motility was defined based on experimentally observed run and tumble behavior. The capillary and bacteria models were combined to simulate the intracapillary transport of bacteria. Non-motile bacteria and nanoparticles of 200 nm, 300 nm, and 405 nm were also simulated in capillary flow for comparison to motile bacteria. Motile bacteria tended to swim into the plasma layer near the capillary wall, while non-motile bacteria tended to get caught in the bolus flow between the RBCs. The nanoparticles were more impacted by Brownian motion and small scale fluid fluctuations, so they did not trend toward a single region of the flow. Motile bacteria were found to have the longest residence time in a 1 mm long capillary as well as the highest average radial velocity. This suggests motile bacteria may enter the interstitium at a higher rate than non-motile bacteria or nanoparticles of diameters between 200–405 nm. / Master of Science / The last 50 years have brought significant advancements in cancer treatment. Despite progress, cancer still remains one of the leading causes of death. In 2016, an estimated 1.7 million new cases of cancer will be diagnosed, and nearly 600,000 people will die from the disease in the United States alone. This is due to numerous unsolved challenges in the field of cancer research. The present study looks at one of these challenges—specially the delivery of drugs into a solid tumor. Several biological factors prohibit chemotherapy drugs from fully penetrating tumors. This prevents the drugs from completely killing the cancer, and can lead to ineffective treatment or recurrence. Innovative new techniques to help drugs better penetrate tumors are under development. One such technique is to harness bacteria to carry drugs inside of tumors. The goal of the present research is to evaluate the behavior of drug carrying bacteria with computer simulations. Blood vessels carry things in and out of tumors. The smallest blood vessels, the capillaries, are the location at which bacteria enter the tumor. The computer simulations found potential for swimming bacteria to enter the tumor at greater rates than other methods of drug delivery. Behavior of bacteria in capillaries is important, but just one of many aspects of this treatment strategy so research is ongoing. Beyond the simulations run for this study, the computer software developed during this project could also have other applications in engineering and biology research.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/77502 |
| Date | 06 October 2016 |
| Creators | Windes, Peter |
| Contributors | Mechanical Engineering, Tafti, Danesh K., Qiao, Rui, Behkam, Bahareh |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | en_US |
| Detected Language | English |
| Type | Thesis, Text |
| Format | application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
Page generated in 0.0121 seconds