Modeling iontophoretic drug delivery in a microfluidic device

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dc.contributor.authorMoarefian, Maryamen
dc.contributor.authorDavalos, Rafael V.en
dc.contributor.authorTafti, Danesh K.en
dc.contributor.authorAchenie, Luke E. K.en
dc.contributor.authorJones, Caroline N.en
dc.contributor.departmentMechanical Engineeringen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentChemical Engineeringen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2020-12-08T14:10:33Zen
dc.date.available2020-12-08T14:10:33Zen
dc.date.issued2020-09-21en
dc.description.abstractIontophoresis 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.en
dc.description.notesResearch materials and equipment for this study were funded by CNJ startup funds from the Department of Biological Sciences at Virginia Tech and The National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM133610. MM was supported by the VT-Initiative for Maximizing Student Development (IMSD) (NIGMS 2R25GM072767-05A1) and the Department of Mechanical Engineering at Virginia Tech.en
dc.description.sponsorshipDepartment of Biological Sciences at Virginia Tech; National Institute of General Medical Sciences of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R35GM133610]; VT-Initiative for Maximizing Student Development (IMSD) (NIGMS) [2R25GM072767-05A1]; Department of Mechanical Engineering at Virginia Tech.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1039/d0lc00602een
dc.identifier.eissn1473-0189en
dc.identifier.issn1473-0197en
dc.identifier.issue18en
dc.identifier.pmid32869052en
dc.identifier.urihttp://hdl.handle.net/10919/101040en
dc.identifier.volume20en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleModeling iontophoretic drug delivery in a microfluidic deviceen
dc.title.serialLab On A Chipen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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