DOI QR코드

DOI QR Code

Quantitative Label-free Terahertz Sensing of Transdermal Nicotine Delivered to Human Skin

  • Lee, Gyuseok (Department of Electrical Engineering, Pohang University of Science and Technology) ;
  • Namkung, Ho (Department of Electrical Engineering, Pohang University of Science and Technology) ;
  • Do, Youngwoong (Department of Electrical Engineering, Pohang University of Science and Technology) ;
  • Lee, Soonsung (Department of Electrical Engineering, Pohang University of Science and Technology) ;
  • Kang, Hyeona (Department of Electrical Engineering, Pohang University of Science and Technology) ;
  • Kim, Jin-Woo (Department of Electrical Engineering, Pohang University of Science and Technology) ;
  • Han, Haewook (Department of Electrical Engineering, Pohang University of Science and Technology)
  • Received : 2020.05.18
  • Accepted : 2020.06.15
  • Published : 2020.08.25

Abstract

We report the terahertz time-domain spectroscopy (THz-TDS) of transdermal drug delivery in human skin. The time evolution of transdermal nicotine delivery in nicotine patches was assessed by detecting the transmission coefficient of sub-picosecond THz pulses and using a semi-analytic model based on the single-layer effective medium approximation. Using commercial nicotine patches (Nicoderm CQ®, 7 mg/24 h), THz transmission coefficients were measured to quantitatively analyze the cumulative amounts of nicotine released from the patches in the absence of their detailed specifications, including multilayer structures and optical properties at THz frequencies. The results agreed well with measurements by conventional in vitro and in vivo methods, using a diffusion cell with high-performance liquid chromatography and blood sampling respectively. Our study revealed the ability of the THz-TDS method to be an effective alternative to existing methods for noninvasive and label-free assessments of transdermal drug delivery, showing its high promise for biomedical, pharmaceutical, and cosmetic applications.

Keywords

References

  1. R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, "Terahertz pulse imaging of ex vivo basal cell carcinoma," J. Invest. Dermatol. 120, 72-78 (2003). https://doi.org/10.1046/j.1523-1747.2003.12013.x
  2. S. W. Smye, J. M. Chamberlain, A. J. Fitzgerald, and E. Berry, "The interaction between Terahertz radiation and biological tissue," Phys. Med. Biol. 46, R101 (2001). https://doi.org/10.1088/0031-9155/46/9/201
  3. E. Jung, H.-J. Choi, M. Lim, H. Kang, H. Park, H. Han, B.-H. Min, S. Kim, I. Park, and H. Lim, "Quantitative analysis of water distribution in human articular cartilage using terahertz time-domain spectroscopy," Biomed. Opt. Express 3, 1110-1115 (2012). https://doi.org/10.1364/BOE.3.001110
  4. E. Jung, H. Park, K. Moon, M. Lim, Y. Do, H. Han, H. J. Choi, B.-H. Min, S. Kim, I. Park, and H. Lim, "THz timedomain spectroscopic imaging of human articular cartilage," J. Infrared, Millimeter, Teraherz Waves 33, 593-598 (2012). https://doi.org/10.1007/s10762-012-9903-0
  5. E.-A. Jung, M.-H. Lim, K.-W. Moon, Y.-W. Do, S.-S. Lee, H.-W. Han, H.-J. Choi, K.-S. Cho, and K.-R. Kim, "Terahertz pulse imaging of micro-metastatic lymph nodes in early-stage cervical cancer patients," J. Opt. Soc. Korea 15, 155-160 (2011). https://doi.org/10.3807/JOSK.2011.15.2.155
  6. P. C. Ashworth, E. Pickwell-MacPherson, E. Provenzano, S. E. Pinder, A. D. Purushotham, M. Pepper, and V. P. Wallace, "Terahertz pulsed spectroscopy of freshly excised human breast cancer," Opt. Express 17, 12444-12454 (2009). https://doi.org/10.1364/OE.17.012444
  7. Z. D. Taylor, R. S. Singh, M. O. Culjat, J. Y. Suen, W. S. Grundfest, H. Lee, and E. R. Brown, "Reflective terahertz imaging of porcine skin burns," Opt. Lett. 33, 1258-1260 (2008). https://doi.org/10.1364/OL.33.001258
  8. K. W. Kim, H. Kim, J. Park, J. K. Han, and J.-H. Son, "Terahertz tomographic imaging of transdermal drug delivery," IEEE Trans. Terahertz Sci. Technol. 2, 99-106 (2012). https://doi.org/10.1109/TTHZ.2011.2177175
  9. J. Wu, K. S. Paudel, C. Strasinger, D. Hammell, A. L. Stinchcomb, and B. J. Hinds, "Programmable transdermal drug delivery of nicotine using carbon nanotube membranes," Proc. Natl. Acad. Sci. U.S.A. 107, 11698-11702 (2010). https://doi.org/10.1073/pnas.1004714107
  10. M. R. Prausnitz and R. Langer, "Transdermal drug delivery," Nat. Biotechnol. 26, 1261-1268 (2008). https://doi.org/10.1038/nbt.1504
  11. OECD, "Section 4: Health Effects," in OECD Guidelines for the Testing of Chemicals (OECD, 2004), Test NO. 428.
  12. T. J. Franz, "Percutaneous absorption. On the relevance of in vitro data," J. Invest. Dermatol. 64, 190-195 (1975). https://doi.org/10.1111/1523-1747.ep12533356
  13. OECD, "Section 4: Health Effects," in OECD Guidelines for the Testing of Chemicals (OECD, 2004), Test NO. 427.
  14. Nicoderm CQ$^{(R)}$, How to use NicoDerm CQ (Nicoderm CQ$^{(R)}$), https://www.nicodermcq.com/about-nicoderm-cq/how-to-usenicoderm-cq.html (Accessed date: 14 May 2020).
  15. Advameg, Inc., Nicotine patch (How Products Are Made), http://www.madehow.com/Volume-3/Nicotine-Patch.html#ixzz47mtvWygA (Accessed date: 14 May 2020).
  16. S. L. Chuang, Physics of Photonic Devices, 2nd ed. (John Wiley&Sons, NJ, USA, 2009), pp. 202-220.
  17. B. Yu, Z. Huang, X.-Y. Wang, and G.-Z. Zhao, "Study on THz spectra of nicotinic acid, nicotinamide and nicotine," Spectrosc. Spectral Anal. 29, 2334-2337 (2009). https://doi.org/10.3964/j.issn.1000-0593(2009)09-2334-04
  18. Y.-S. Jin, G.-J. Kim, and S.-G. Jeon, "Terahertz dielectric properties of polymers," J. Korean Phys. Soc. 49, 513-517 (2006).
  19. S. K. Gupta, N. L. Benowitz, P. Jacob 3rd, C. N. Rolf, and J. Gorsline, "Bioavailability and absorption kinetics of nicotine following application of a transdermal system," Br. J. Clin. Pharmacol. 36, 221-227 (1993). https://doi.org/10.1111/j.1365-2125.1993.tb04221.x