@article{RN126,
   author = {Moarefian, M. and Davalos, R. V. and Tafti, D. K. and Achenie, L. E. and Jones, C. N.},
   title = {Modeling iontophoretic drug delivery in a microfluidic device},
   journal = {Lab Chip},
   volume = {20},
   number = {18},
   pages = {3310-3321},
   note = {1473-0189
Moarefian, Maryam
Davalos, Rafael V
Tafti, Danesh K
Achenie, Luke E
Jones, Caroline N
R25 GM072767/GM/NIGMS NIH HHS/United States
R35 GM133610/GM/NIGMS NIH HHS/United States
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
England
2020/09/02
Lab Chip. 2020 Sep 21;20(18):3310-3321. doi: 10.1039/d0lc00602e. Epub 2020 Sep 1.},
   abstract = {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-MB-231 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®) to the actual concentration in the microfluidic device. Alexa Fluor 594® 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.},
   keywords = {Drug Delivery Systems
*Iontophoresis
Lab-On-A-Chip Devices
*Pharmaceutical Preparations/metabolism
Skin/metabolism
Skin Absorption},
   ISSN = {1473-0197 (Print)
1473-0189},
   DOI = {10.1039/d0lc00602e},
   year = {2020},
   type = {Journal Article}
}

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N."],"bibdata":{"bibtype":"article","type":"Journal Article","author":[{"propositions":[],"lastnames":["Moarefian"],"firstnames":["M."],"suffixes":[]},{"propositions":[],"lastnames":["Davalos"],"firstnames":["R.","V."],"suffixes":[]},{"propositions":[],"lastnames":["Tafti"],"firstnames":["D.","K."],"suffixes":[]},{"propositions":[],"lastnames":["Achenie"],"firstnames":["L.","E."],"suffixes":[]},{"propositions":[],"lastnames":["Jones"],"firstnames":["C.","N."],"suffixes":[]}],"title":"Modeling iontophoretic drug delivery in a microfluidic device","journal":"Lab Chip","volume":"20","number":"18","pages":"3310-3321","note":"1473-0189 Moarefian, Maryam Davalos, Rafael V Tafti, Danesh K Achenie, Luke E Jones, Caroline N R25 GM072767/GM/NIGMS NIH HHS/United States R35 GM133610/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2020/09/02 Lab Chip. 2020 Sep 21;20(18):3310-3321. doi: 10.1039/d0lc00602e. Epub 2020 Sep 1.","abstract":"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-MB-231 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®) to the actual concentration in the microfluidic device. Alexa Fluor 594® 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.","keywords":"Drug Delivery Systems *Iontophoresis Lab-On-A-Chip Devices *Pharmaceutical Preparations/metabolism Skin/metabolism Skin Absorption","issn":"1473-0197 (Print) 1473-0189","doi":"10.1039/d0lc00602e","year":"2020","bibtex":"@article{RN126,\n author = {Moarefian, M. and Davalos, R. V. and Tafti, D. K. and Achenie, L. E. and Jones, C. N.},\n title = {Modeling iontophoretic drug delivery in a microfluidic device},\n journal = {Lab Chip},\n volume = {20},\n number = {18},\n pages = {3310-3321},\n note = {1473-0189\nMoarefian, Maryam\nDavalos, Rafael V\nTafti, Danesh K\nAchenie, Luke E\nJones, Caroline N\nR25 GM072767/GM/NIGMS NIH HHS/United States\nR35 GM133610/GM/NIGMS NIH HHS/United States\nJournal Article\nResearch Support, N.I.H., Extramural\nResearch Support, Non-U.S. Gov't\nEngland\n2020/09/02\nLab Chip. 2020 Sep 21;20(18):3310-3321. doi: 10.1039/d0lc00602e. Epub 2020 Sep 1.},\n abstract = {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-MB-231 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®) to the actual concentration in the microfluidic device. Alexa Fluor 594® 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. 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