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Monitoring drug pharmacokinetics and immunologic biomarkers in dermal interstitial fluid using a microneedle patch

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Abstract

Minimally invasive point-of-care diagnostic devices are of great interest for rapid detection of biomarkers in diverse settings. Although blood is the most common source of biomarkers, interstitial fluid (ISF) is an alternate body fluid that does not clot or contain red blood cells that often complicate analysis. However, ISF is difficult to collect. In this study, we assessed the utility of a microneedle patch to sample microliter volumes of ISF in a simple and minimally invasive manner. We demonstrated the use of ISF collected in this way for therapeutic drug monitoring by showing similar vancomycin pharmacokinetic profiles in ISF and serum from rats. We also measured polio-specific neutralizing antibodies and anti-polio IgG in ISF similar to serum in rats immunized with polio vaccine. These studies demonstrate the potential utility of ISF collected by microneedle patch in therapeutic drug monitoring and immunodiagnostic applications.

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References

  • N.L. Anderson, N.G. Anderson, Mol. Cell. Proteomics 1(11), 845 (2002)

    Google Scholar 

  • C.R. Laboratories, https://www.criver.com/sites/default/files/resources/BaselineHematologyandClinicalChemistryValuesforCharlesRiverWistarRats%5BCrlWIBR%5DasaFunctionofSexandAgeSpring1998.pdf. (Accessed 18 April 2018)

  • E. Caffarel-Salvador, A.J. Brady, E. Eltayib, T. Meng, A. Alonso-Vicente, P. Gonzalez-Vazquez, B.M. Torrisi, E.M. Vicente-Perez, K. Mooney, D.S. Jones, PLoS One 10(12), e0145644 (2015)

    Google Scholar 

  • J.E. Celis, P. Gromov, T. Cabezón, J.M. Moreira, N. Ambartsumian, K. Sandelin, F. Rank, I. Gromova, Mol. Cell. Proteomics 3(4), 327 (2004)

    Google Scholar 

  • H. Chang, M. Zheng, X. Yu, A. Than, R.Z. Seeni, R. Kang, J. Tian, D.P. Khanh, L. Liu, P. Chen. Adv. Mater. 29(37) (2017)

  • J.W. Coffey, S.C. Meliga, S.R. Corrie, M.A. Kendall, Biomaterials84, 130 (2016)

    Google Scholar 

  • B. Deacon, J. Abramowitz, J. Anxiety Disord. 20(7), 946 (2006)

    Google Scholar 

  • R.F. Donnelly, K. Mooney, E. Caffarel-Salvador, B.M. Torrisi, E. Eltayib, J.C. McElnay, Ther. Drug Monit. 36(1), 10 (2014)

    Google Scholar 

  • G.J. Downing, Biomarkers: Facing the Challenges at the Crossroads of Research and Health Care, Pharmaceutical Science Encyclopedia, John Wiley & Sons, Inc., pp. 1 (2010)

  • C. Edens, N.C. Dybdahl-Sissoko, W.C. Weldon, M.S. Oberste, M.R. Prausnitz, Vaccine 33(37), 4683 (2015)

    Google Scholar 

  • A. El-Laboudi, N.S. Oliver, A. Cass, D. Johnston, Diabetes Technol. Ther. 15(1), 101 (2013)

    Google Scholar 

  • D.J. Finney, Statistical Method in Biological Assay, Charles Griffin: London (1952)

  • F.T. Fischbach, M.B. Dunning, A manual of laboratory and diagnostic tests, Lippincott Williams & Wilkins (2009)

  • N. Fogh-Andersen, B.M. Altura, B.T. Altura, O. Siggaard-Andersen, Clin. Chem. 41(10), 1522 (1995)

    Google Scholar 

  • S.K. Garg, R.O. Potts, N.R. Ackerman, S.J. Fermi, J.A. Tamada, H.P. Chase, Diabetes Care 22(10), 1708 (1999)

    Google Scholar 

  • S.A. Geherin, S.R. Fintushel, M.H. Lee, R.P. Wilson, R.T. Patel, C. Alt, A.J. Young, J.B. Hay, G.F. Debes, J. Immunol. 1102639 (2012)

  • B. Greenwood, A. Hall, M. Rowe, H. Whittle, M. George, A. Al-Ghassani, M. Elbualy, P. Malankar, A. Suleiman, G. Clements, Bull. World Health Organ. 74, 253 (1996)

    Google Scholar 

  • J. Hadrévi, B. Ghafouri, A. Sjörs, H. Antti, B. Larsson, A. Crenshaw, B. Gerdle, F. Hellström, Eur. J. Appl. Physiol. 113(12), 2977 (2013)

    Google Scholar 

  • Y. Hamada, J.L. Kuti, D.P. Nicolau, J. Antimicrob. Chemother.70(7), 2064 (2015)

    Google Scholar 

  • C. Herkenne, I. Alberti, A. Naik, Y.N. Kalia, F.-X. Mathy, V. Préat, R.H. Guy, Pharm. Res. 25(1), 87 (2008)

    Google Scholar 

  • S.T. Housman, A.A. Bhalodi, A. Shepard, J. Nugent, D.P. Nicolau, J. Am. Podiatr. Med. Assoc. 105(5), 381 (2015)

    Google Scholar 

  • Y. Ito, Y. Inagaki, S. Kobuchi, K. Takada, T. Sakaeda, Int. J. Med. Sci. 13(4), 271 (2016)

    Google Scholar 

  • T.K. Kiang, V. Schmitt, M.H. Ensom, B. Chua, U.O. Häfeli, J. Pharm. Sci. 101(12), 4642 (2012)

    Google Scholar 

  • T.K. Kiang, U.O. Häfeli, M.H. Ensom, Clin. Pharmacokinet. 53(8), 695 (2014)

    Google Scholar 

  • U. Kiistala, K. Mustakallio, J. Investig. Dermatol. 48(5), 466 (1967)

    Google Scholar 

  • M. Lindberger, T. Tomson, L. Ståhle, Basic Clin. Pharmacol. Toxicol. 91(4), 158 (2002)

    Google Scholar 

  • D. Loewenstein, C. Stake, M. Cichon, Am. J. Emerg. Med. 31(8), 1236 (2013)

    Google Scholar 

  • D. Mabey, R.W. Peeling, A. Ustianowski, M.D. Perkins, Nat. Rev. Microbiol. 2(3), 231 (2004)

    Google Scholar 

  • P.R. Miller, S.D. Gittard, T.L. Edwards, D.M. Lopez, X. Xiao, D.R. Wheeler, N.A. Monteiro-Riviere, S.M. Brozik, R. Polsky, R.J. Narayan, Biomicrofluidics 5(1), 013415 (2011)

    Google Scholar 

  • P.R. Miller, S.A. Skoog, T.L. Edwards, D.M. Lopez, D.R. Wheeler, D.C. Arango, X. Xiao, S.M. Brozik, J. Wang, R. Polsky, Talanta 88, 739 (2012)

    Google Scholar 

  • P.R. Miller, X. Xiao, I. Brener, D.B. Burckel, R. Narayan, R. Polsky, Adv. Healthcare Mater. 3(6), 876 (2014)

    Google Scholar 

  • A.C. Müller, F.P. Breitwieser, H. Fischer, C. Schuster, O. Brandt, J. Colinge, G. Superti-Furga, G. Stingl, A. Elbe-Bürger, K.L. Bennett, J. Proteome Res. 11(7), 3715 (2012)

    Google Scholar 

  • D.A. Muller, S.R. Corrie, J. Coffey, P.R. Young, M.A. Kendall, Anal. Chem. 84(7), 3262 (2012)

    Google Scholar 

  • J. Nachbaur, M. Clarke, J. Provost, J. Dancla, Lab. Anim. Sci.27(6), 972 (1977)

    Google Scholar 

  • M.M. Niedzwiecki, P. Samant, D.I. Walker, V. Tran, D.P. Jones, M.R. Prausnitz, G.W. Miller, Anal. Chem. 90(6), 3786 (2018)

    Google Scholar 

  • S. Pichini, I. Altieri, P. Zuccaro, R. Pacifici, Clin. Pharmacokinet. 30(3), 211 (1996)

    Google Scholar 

  • S.A. Plotkin, W.A. Orenstein, P.A. Offit, Vaccines, Saunders (2004)

  • M.R. Prausnitz, Annu. Rev. Chem. Biomol. Eng. 8, 177 (2017)

    Google Scholar 

  • E. Renard, Curr. Diabetes Rev. 4(3), 169 (2008)

    Google Scholar 

  • M.J. Rybak, Clin. Infect. Dis. 42(Supplement_1), S35 (2006)

    Google Scholar 

  • M. Rybak, B. Lomaestro, J.C. Rotschafer, R. Moellering, W. Craig, M. Billeter, J.R. Dalovisio, D.P. Levine, Am. J. Health Syst. Pharm. 66(1), 82 (2009)

    Google Scholar 

  • P.P. Samant, M.R. Prausnitz, Proc. Natl. Acad. Sci. 115, 4583 (2018)

    Google Scholar 

  • S. Schmidt, R. Banks, V. Kumar, K.H. Rand, H. Derendorf, J. Clin. Pharmacol. 48(3), 351 (2008)

    Google Scholar 

  • A. Sieg, R.H. Guy, M.B. Delgado-Charro, Clin. Chem. 50(8), 1383 (2004)

    Google Scholar 

  • C.H. Sloop, L. Dory, P.S. Roheim, J. Lipid Res. 28(3), 225 (1987)

    Google Scholar 

  • P. Stetina, B. Madai, V. Kulemann, W. Kirch, C. Joukhadar, Int. J. Clin. Pharmacol. Ther. 43(3), 134 (2005)

    Google Scholar 

  • H. Suh, J. Shin, Y.-C. Kim, Clin. Exp. Vaccine Res. 3(1), 42 (2014)

    Google Scholar 

  • B.Q. Tran, P.R. Miller, R.M. Taylor, G. Boyd, P.M. Mach, C.N. Rosenzweig, J.T. Baca, R. Polsky, T. Glaros, J. Proteome Res. 17(1), 479 (2017)

    Google Scholar 

  • M. Venugopal, K.E. Feuvrel, D. Mongin, S. Bambot, M. Faupel, A. Panangadan, A. Talukder, R. Pidva, IEEE Sensors J. 8(1), 71 (2008)

    Google Scholar 

  • A. Vrdoljak, E.A. Allen, F. Ferrara, N.J. Temperton, A.M. Crean, A.C. Moore, J. Control. Release 225, 192 (2016)

    Google Scholar 

  • H. Wiig, O. Tenstad, P.O. Iversen, R. Kalluri, R. Bjerkvig, Fibrog. Tissue Repair 3(1), 12 (2010)

    Google Scholar 

  • P. Yager, G.J. Domingo, J. Gerdes, Annu. Rev. Biomed. Eng.10, 107 (2008)

    Google Scholar 

  • Y. Ye, J. Yu, D. Wen, A.R. Kahkoska, Z. Gu, Adv. Drug Deliv. Rev.127, 106 (2018)

    Google Scholar 

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Acknowledgments

The authors would like to thank William Weldon of the CDC for conducting serum and ISF neutralizing antibody assays and Donna Bondy for administrative support. Mark Prausnitz is an inventor of patents that have been or may be licensed to companies developing microneedle-based products, is a paid advisor to companies developing microneedle-based products and is a founder/shareholder of companies developing microneedle-based products, including Micron Biomedical. These potential conflicts of interest have been disclosed and are being managed by Georgia Tech and/or Emory University.

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Authors and Affiliations

  1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 315 Ferst Drive, Atlanta, GA, 30332, USA

    Chandana Kolluru, Mikayla Williams & Mark R. Prausnitz

  2. School of Pharmaceutical Sciences, Mercer University, Atlanta, GA, 30341, USA

    Jihee Stephanie Yeh & Jennifer Knaack

  3. Physiological Research Laboratory, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA, 30332, USA

    Richard K. Noel

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  1. Chandana Kolluru
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Correspondence to Mark R. Prausnitz.

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Kolluru, C., Williams, M., Yeh, J.S. et al. Monitoring drug pharmacokinetics and immunologic biomarkers in dermal interstitial fluid using a microneedle patch. Biomed Microdevices 21, 14 (2019). https://doi.org/10.1007/s10544-019-0363-3

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