BEE 4530 - 2016 Student Papers

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Optimization of Contact Lens Drug Delivery to Ocular Tissue
Barsoum, Kyrollos; Kureshi, Rakeeb; Lee, Carina; Pacifici, Noah (2016-05-16)
Intraocular pressure is a risk factor for developing glaucoma, a disease that damages the optic nerve and can result in vision impairment. Timolol is a beta-adrenergic antagonist that decreases intraocular pressure (IOP) by reducing the epithelial production of aqueous humor in the ciliary body. Traditionally, Timolol medication is administered with eye drops, but this treatment results in low corneal bioavailability and residence time of the drug in the ciliary muscle, making eye drops an inefficient method of drug delivery. In addition, eye drops lead to a higher concentration of Timolol in the systemic circulation, which can cause potential side effects. However, contact lenses soaked in Timolol solution can increase the bioavailability of the drug and drug release duration, therefore improving glaucoma treatment while decreasing the amount of drug absorbed into systemic circulation and unwanted side effects. The purpose of our study was to optimize the residence time of Timolol in the ciliary muscle at its effective concentration by optimizing the initial concentration in the soaked contact lens. We presented a model of drug diffusion from the contact lens through the cornea and aqueous humor to the ciliary body epithelium. Using COMSOL, the diffusion of Timolol through the contact lens, cornea, aqueous humor, and ciliary muscle was modeled using a mass transfer equation. Additionally, fluid flow and natural heat convection in the aqueous humor was accounted for in the model, and these governing equations were coupled to the equation for mass transfer of Timolol in the domain. The eye was simplified to a 2-dimensional axisymmetric spherical geometry. We aimed to solve for the optimal initial concentration of Timolol in the contact lens, given the ideal concentration in the ciliary body epithelium, which is a value that was found in the literature. In our 2-dimensional axisymmetric model, we demonstrated using our computer simulation that, in order to optimize the residence time of Timolol in the ciliary muscle at its most effective concentration, the initial concentration in the soaked contact lens must be 6.25 · 10−5 mol/m3. The mass diffusion of Timolol was not only driven by diffusion but also convective fluid flow. Fluid flow was introduced by a temperature gradient in the eye and resulted in a density gradient. Additionally, we performed several sensitivity analyses to determine which parameters affected the concentration of Timolol. Changing the ambient air temperature did not affect the uptake of Timolol in the ciliary muscle. The Peclet number indicates the importance of convection with respect to conduction and it was found to indicate that convection had a greater affect on Timolol transport than conduction. Additionally, the diffusivity of the contact lens also influenced the amount of Timolol delivered to the ciliary muscle. Thus, the concentration of Timolol in the ciliary muscle is highly sensitive to variations in convection and diffusivity parameters. In this model, we reinforced the validity of using computer simulations to model ocular drug delivery using a contact lens as a drug delivery platform. The parameters and variables of this model can be modified to account for different dosage requirements and different boundary or environmental conditions, making our model a viable way to speed up the design process by running the simulation instead of experimentally testing contact lenses with varying parameters. Our model is applicable to any drug that can be administered by contact lens and will reduce drug testing time and significantly reduce costs during the approval process.
Procoagulant Microparticle Interactions Due to P-sel-Ig in Hemophilia A Patients
Lin, Iris; Waidyaratne, Gavisha; Chainani, Masoom; Venosa, Ethan (2016-05-16)
Congenital hemophilia is a hereditary, X-linked blood-clotting disease that involves insufficient clotting factors VIII and IX. There are two types of hemophilia, Hemophilia A and Hemophilia B. Hemophilia A is the most common form of hemophilia affecting individuals. Current treatment options include recombinant or concentrated plasma procoagulant. However, immunity to these treatment options as well as high treatment cost is common. This research models a treatment option involving P-selectin. P-selectin is a known precursor to tissue clotting factors already present in the body, and therefore can minimize the issue of immunity to treatment. The purpose of this research is to optimize the delivery of a P-selectin precursor in order to minimize clotting time and reduce immunity to drug therapy for hemophilia patients. In order to simulate this treatment, the drug P-sel-Ig was assumed to have been injected and reacted within the vein to produce an initial steadystate microparticle concentration. In COMSOL, as mass transport through a cylindrical vessel with fluid flow. This model measures the time it takes to accumulate enough fibrin to fully clot the wound. The model also optimizes microparticle concentration to minimize the time taken to clot the wound. The model can be adjusted for varying wound size, location, and time of formation. This model was validated in optimizing microparticle concentration for promoting the clotting of wounds. The literature value for wound clotting time is approximately 4.5 minutes. In order to achieve a complete wound clot, the clotting time from the model was approximately 35 minutes, which is within an order of magnitude from the literature value. This research defines clotting time as the number of minutes necessary to reach a 90% threshold fibrin density packing ratio. The optimal initial microparticle concentration was 2.66×10 5 mol/m 3 . In addition, the model showed that as wound size increases, the time necessary to close the wound also increases. The computation model demonstrated a range of initial microparticle concentrations necessary to provide adequate fibrin clot formation in response to the wound. The results of this model can potentially be used in optimizing the design of a regularly administered drug therapy for hemophilia patients to facilitate efficient clotting. This drug therapy would be cheaper treatment option because of its longer halflife. It would also prevent the formation of antibodies, which reduces the effectiveness of current treatment options.
Finite Element Modeling of Thermal Regulation in Extra Vehicular Activity
Biswas, Rohit; France, Emma; Paradkar, Mihir; Woods, Zach (2016-05-16)
Astronauts perspire heavily during the strenuous exercise of Extravehicular Activity (EVA), and previous literature has expressed concern that this may negatively impact the ability of the LCVG to maintain thermal comfort. However, thorough testing of EVA suits on Earth is nearly impossible due to difficulty in replicating the harsh conditions of space. This project strived to alleviate the necessity of physical simulation with a computer-based model using the software package COMSOL. The model was designed to simulate the fluid and heat transfer dynamics in EVA suits. In particular, we examined the suit’s Liquid Cooling and Ventilation Garment (LCVG), an inner layer of fabric and coolant tubing that regulates astronaut body temperature. We modeled leakage of perspiration into this fabric layer, creating space- and time-dependent heat flow properties in the system. We used both a 2D simplified geometry and a realistic humanoid 3D geometry to balance physical accuracy requirements with available computational power. We show that skin temperature in anatomical locations of heavy perspiration varies more than in drier locations. We also show that the skin surface temperature is maintained at a comfortable level by the LCVG even during swings in levels of external radiative heating. Finally, we show that a varying metabolic rate corresponds to variations in skin temperature with time. Skin surface temperature and its control have implications for both astronaut comfort and LCVG efficiency. We have shown that it is possible to study the effects of various parameters on skin temperature using a simple finite element model. This enables safer and more comfortable suit design without the undue time, cost, and complexity of full physical testing. We have also shown that the effects of perspiration can be consequential, and are worth exploration in further research.
Cupric Ion Release from Various IUD Geometries
Hernández, Sascha; Riggs, Lauren; Widjaja, Edison (2016-05-16)
Intrauterine Devices (IUDs) are gaining popularity as a form of long-acting reversible contraceptives (LARC); once inserted, copper IUDs can be effective for up to ten years and require no action from the user. The contraceptive effect of copper IUDs is believed to be at least partially due to the spermicidal effect of cupric ions in the uterine cavity, as well as the inflammatory immune response induced by the foreign object. The release of cupric ions depends on the surface area of copper, IUD geometry and physiological factors. Negative side effects from IUDS, such as pain and bleeding, are also related to IUD shape and uterine anatomy. There has been increased interest in developing new IUD designs that minimize these unwanted side effects while maintaining contraceptive effectiveness. In order to implement new IUD designs, animal testing and clinical trials are stages in which prototypes are determined to be effective. To minimize risk, a computer-simulated model can predict how an IUD will behave in vivo. However, a computer-simulated model of cupric ion release from IUDs does not presently exist. Therefore, this study accomplished the goal of developing a physiologically accurate digital model of cupric IUD erosion patterns in the uterus. By using COMSOL, a physiologically accurate model of an IUD in vivo was created. Then, the diffusion behavior of copper in two different domains – the uterine fluid and the blood – was simulated. Because the copper IUD will release copper ions as it erodes, the concentrations of copper in the two domains were dependent on the mass flux of copper out of the IUD. The concentration of copper in these domains was also affected by copper removal, which occurs through convective flux in the blood and cervical flux. The concentration of copper ions in the uterine fluid and blood were tracked over a period of 1 year. As a result, this model allowed investigators to determine the parameters at which a digitally modeled copper IUD is most physiologically accurate. The T-shaped copper IUD can be accurately modeled in COMSOL by using accurate parameters and incorporating a periodic function for increases in copper flux throughout the menstrual cycle.
Endovenous Laser Treatment for Occlusion of Varicose Veins
Bai, Lillia; Cullopulli, Sherya; Nadeau, Sarah (2016-05-16)
Endovenous laser treatment (ELT) is a minimally invasive technique that uses laser energy to treat varicose veins. An optical fiber is inserted under the guidance of ultrasound and laser light is shone into the interior of the varicose vein. The optical fiber is withdrawn at a constant rate as, simultaneously, contraction of the vein occurs in response to heating induced by laser light exposure. Our goal is to model heat transfer between the laser and the vein wall and optimize laser power and pullback speed for ELT. Modeling was performed in COMSOL using Navier-Stokes fluid flow and transient state heat transfer. The problem geometry was simplified to a 2D axisymmetric model consisting of a lumen, vein wall and perivenous tissue. By modeling the ELT process, we were easily able to observe temperature changes and quantify cell death, a measure of tissue damage, in the vein wall and perivenous tissue while manipulating laser power and pullback speed. We analyzed cell death in the vein wall, where permanent damage is desirable, as compared to the perivenous tissue, where it is not, at various laser powers and pullback speeds. Our results indicate that several optimal laser power and pullback speed combinations exist for different criteria. For minimum damage to the perivenous tissue we recommend a laser power of 15 W and a pullback speed of 2 mm/s. If damage to approximately 100 mm2 of perivenous tissue is acceptable, the maximum amount of vein wall tissue can be destroyed using a laser power of 30 W and a pullback speed of 4 mm/s. Our model supports the effectiveness of the ELT procedure and enhances discussions on best treatment methods. Optimization of laser power and pullback speed improves the efficacy of the treatment and decreases risk associated with damage to the perivenous tissue. By improving the efficacy and safety of ELT we hope to improve treatment options for the vast number of people suffering from varicose veins. Our results may also be used as foundation for further comparative studies of ELT procedure.
Breaking the Skin Barrier: Modelling Microneedles for Transdermal Insulin Delivery
Kang, Jeniffer; Lee, Amy; Lee, Julie; Sadikin, Felicia (2016-05-16)
Transdermal patches, devices developed to deliver drugs, can be limited in their efficacy because the amount of drug that diffuses through the skin often doesn’t reach sufficient concentrations. This problem is alleviated by using the ‘poke with patch’ method, which uses a patch with microneedles to puncture the skin in order to help increase drug penetration through the skin. In our project, we investigated varying number of punctures and modeled how that impacts drug diffusion through the skin over time. We modeled this system in COMSOL as a 2D slab representing the multiple layers within the skin, and simulated insulin flow from the patch into the capillary blood layer. To study the effect of the number of punctures on drug delivery, we created four models with 5, 10, 20, and 50 microneedle punctures. We then gathered data of insulin concentrations over 24 hours at two different points in the geometry—underneath a microneedle and at the exit of the blood domain—as well as in the drug patch and in the body. The data gathered from all four models were then evaluated to find the trends. The data collected showed that as we increase the number of microneedles in the patch, the insulin concentration underneath the needle decreases. However, with a greater number of microneedles, the insulin concentration exiting the blood domain significantly increases, and insulin exits the drug patch at a faster rate. From our results, we see that the addition of microneedle punctures improves the efficacy of transdermal patches by increasing the insulin delivered into the body through the patch. Since insulin concentration in the blood increases when there are more microneedles in the patch, we can conclude that increasing the number of microneedle punctures optimizes drug delivery. However, there should be a limit on the number of punctures to prevent potential clinical damage to the skin.
A Computer Model for Evaluating the Efficiency of Cryosurgery for Prostate Cancer
Horsfield, Michael; Sarkar, Ritvik; Reffsin, Sam; Seog, Woo Jin (2016-05-16)
We model the effects of the cryosurgery process for prostate cancer in COMSOL Multiphysics® (ver 5.1) using imaging and manufacturing data to generate 3D realistic geometry for the prostate and cryoprobe. By imposing a freezing temperature at the probe-tumor boundary, we can observe the impact on healthy tissue over the freeze-thaw cycles of the surgery procedure. By varying the number and locations of probes, as well as the rate of the freeze-thaw cycle, we find the optimum cryosurgery procedure that kills as much cancer as possible while minimizing damage to the remainder of the prostate. We find that, for an “average” spherical tumor roughly 1 cm in radius found in the center of the prostate, a single probe piercing the tumor’s center fully treats the cancerous tissue without harming healthy tissue more than 1 mm away from the tumor’s edge. This assumes two freeze-thaw cycles at -196°C. This proves that the simulation methodology can predict the optimum surgery procedure. With proper imaging data, this same procedure can be used to treat individuals with differently-shaped and oriented prostate tumors.
Modeling Carmustine Diffusion from Gliadel® Wafers in the Brain to Optimize Cancer Treatment and Minimize Damage to Healthy Tissue
Azar, Julian; Elacqua, Joshua; Peñaranda, David; Stone, Alexander (2016-05-16)
Gliadel® wafers have been developed to circumvent traditional obstacles in brain cancer treatment. Chemotherapeutic drugs administered intravenously are rendered largely ineffective by the blood-brain barrier. Gliadel wafers can be implanted at the tumor removal site during surgery. These wafers then secrete carmustine (also commonly referred to as BCNU) directly into the remaining tumor tissue. Treatment via Gliadel wafers has been widely successful. However, treatment using carmustine can also cause a variety of serious side effects. Thus, we developed a model to examine the efficacy of Gliadel wafers and improve administration of carmustine to the tumor while minimizing damage to healthy tissue and the occurrence of harmful side effects. The transient diffusion of carmustine from wafers in a realistic, three-dimensional brain geometry was examined using COMSOL®. A zero flux boundary condition was used to represent the blood-brain barrier. Blood flow in the brain and degradation of the drug in both the tumor layer and healthy brain tissue were also considered. Optimal wafer properties were then determined to achieve high carmustine concentrations in the leftover tumor and low concentrations in the healthy tissue.
Drug Delivery from PLGA-Coated Stents: Optimization of Strut Geometry and Extent of Embedment in the Arterial Wall
Ernst, Alexander; Gainey, Shelby; Jusuf, Sebastian; Li, Jingrui (2016-05-16)
Patients with atherosclerosis experience plaque buildup in the coronary artery, reducing blood flow and increasing the likelihood of a blood clot. Balloon angioplasty and the implantation of a metal stent are physical mechanisms that have been used to treat atherosclerosis and the associated stenosis of the coronary artery with some success; however, restenosis occurs in a substantial amount of patients. Most recently, biodegradable drug eluting stents have been shown to significantly lower restenosis rates, where an implanted stent is coated with biodegradable polymer and an immunosuppressant therapeutic drug; however, many parameters have yet to be optimized in this method of treatment. This project considers a stent coated with the biodegradable polymer poly lactic-coglycolic acid (PLGA) and immunosuppressant sirolimus (also known as rapamycin), for circular and square geometries, and half and full extents of embedment. A mass transport simulation in COMSOL 5.1 Multiphysics was used to quantitatively simulate this process with the objective of optimizing these design options with respect to drug delivery. Further, this project aimed to suggest potential improvement to current stent designs. Our model showed that the fully embedded stent resulted a significantly higher concentration profile over a 50-day period for both geometries. Likewise, the square model resulted in a slightly preferred elution profile than the circular model for both extents of embedment. The major limitation of the half-embedded model was loss of drug to the bloodstream; hence, we propose two models for improvement: (1) creating an impermeable membrane at the coating-bloodstream interface, and (2) exclusively coating the half of the stent that is in contact with the arterial wall. Design 1 resulted in a significantly increased spatially averaged concentration profile in the arterial wall at all time points in comparison with the benchmark model, and design 2 showed similar profile to the benchmark, despite containing half the mass of drug.
Modeling the Cornea During Laser Ablation Procedures
Anderson, Tyler; Cheng, Pui Lam; Gautier, Thomas; Li, Rebecca (2016-05-16)
Photorefractive keratectomy (PRK) is a form of laser eye surgery used to correct vision. This procedure entails the precise removal of corneal tissue by laser ablation. It has been shown experimentally that dehydration of the corneal tissue leads to a higher dry mass ablation rate, which can lead to longer healing times and imprecise reshaping. In order to maximize surgical accuracy, it is important to know the relationship between tissue ablation rate and corneal hydration. Our model used the computational design software COMSOL 5.1 to model corneal heat and hydration levels during a simulated PRK procedure. We simulated heat and mass transfer under the specified conditions of the eye and laser. Although simplifications must be made from reality, computer-aided modeling allows us to obtain approximate results difficult to obtain in vivo. Consequently, the theoretical corneal hydration after removal of the epithelium and during laser ablation heating can be visualized. This model will be useful alongside experimental trials for improving the success of laser eye surgeries. This model was validated and showed high levels of consistency with past work and other simulations of the cornea during similar procedures. Additionally, this paper proposes one method that may be used to optimize laser ablation procedures by creating a constant ablation rate throughout the procedure. Further work may include finer time steps for time convergence, finer laser pulses, and a longer procedure time.

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