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Scholarly Works, Biomedical Engineering and Mechanics

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https://hdl.handle.net/10919/24286
Research articles, presentations, and other scholarship

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Browsing Scholarly Works, Biomedical Engineering and Mechanics by Author "Achenie, Luke E. K."

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    Modeling iontophoretic drug delivery in a microfluidic device
    Moarefian, Maryam; Davalos, Rafael V.; Tafti, Danesh K.; Achenie, Luke E. K.; Jones, Caroline N. (2020-09-21)
    Iontophoresis employs low-intensity electrical voltage and continuous constant current to direct a charged drug into a tissue. Iontophoretic drug delivery has recently been used as a novel method for cancer treatment in vivo. There is an urgent need to precisely model the low-intensity electric fields in cell culture systems to optimize iontophoretic drug delivery to tumors. Here, we present an iontophoresis-on-chip (IOC) platform to precisely quantify carboplatin drug delivery and its corresponding anti-cancer efficacy under various voltages and currents. In this study, we use an in vitro heparin-based hydrogel microfluidic device to model the movement of a charged drug across an extracellular matrix (ECM) and in MDA-MB231 triple-negative breast cancer (TNBC) cells. Transport of the drug through the hydrogel was modeled based on diffusion and electrophoresis of charged drug molecules in the direction of an oppositely charged electrode. The drug concentration in the tumor extracellular matrix was computed using finite element modeling of transient drug transport in the heparin-based hydrogel. The model predictions were then validated using the IOC platform by comparing the predicted concentration of a fluorescent cationic dye (Alexa Fluor 594 (R)) to the actual concentration in the microfluidic device. Alexa Fluor 594 (R) was used because it has a molecular weight close to paclitaxel, the gold standard drug for treating TNBC, and carboplatin. Our results demonstrated that a 50 mV DC electric field and a 3 mA electrical current significantly increased drug delivery and tumor cell death by 48.12% +/- 14.33 and 39.13% +/- 12.86, respectively (n = 3, p-value <0.05). The IOC platform and mathematical drug delivery model of iontophoresis are promising tools for precise delivery of chemotherapeutic drugs into solid tumors. Further improvements to the IOC platform can be made by adding a layer of epidermal cells to model the skin.
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    A passive diffusion model of fluorescein derivatives in an in vitro human brain microvascular endothelial cell (HBMEC) monolayer
    Simmons, Jamelle M.; Lee, Yong Woo; Achenie, Luke E. K. (JVE, 2018-09-29)
    Eukaryotic cells have a protective plasma membrane, which restricts the free movement of molecules from the external environment to the internal environment. This study aims to computationally model the transport of fluorescein derivatives across the monolayer of human brain microvascular endothelial cells (HBMEC). The determination of plausible effective diffusion constants (𝐷eff) will allow models to be built that could be useful beyond in vitro experimentation. Fluorescein-5-isothiocyanate (FITC) modeling produced a 𝐷effrange of 1E-20 to 5E-20 cm²/s at a 1 μm cell monolayer thickness and a 𝐷eff constant near 5E-29 cm²/s at a 5 μm cell monolayer thickness. Both fluorescein and sodium fluorescein (NaFl) modeling at the 1 and 5 μm thicknesses did not produce simulations that closely resembled the HBMEC in vitro model. Overall, it is possible that the fluorescent intensity noted with fluorescein and NaFl may be better explained by a mechanism other than passive diffusion. Simulations of FITC diffusion produced a narrow range of 𝐷eff constants that closely matched the in vitro HBMEC fluorescent intensity.