Advertisement

Annals of Biomedical Engineering

, Volume 46, Issue 12, pp 2012–2022 | Cite as

Optimal Design of Needle Array for Effective Drug Delivery

  • Hanwook Park
  • Hyejeong Kim
  • Sang Joon Lee
Article
  • 80 Downloads

Abstract

Recently, the multi-needle drug injection has been adopted to overcome the shortcomes of conventional single-needle injection, enhancing the efficiency of drug delivery. However, the effect of needle array on the efficacy of drug delivery has not been fully elucidated. In this study, the interactions of drug analogous solution injected from a pair of needles were analyzed to examine the design criteria of effective multi-needle devices for drug delivery. Temporal and spatial variations of relative contents of the solution in the tissues were compared according to the distance between two adjacent needles (DN). As the DN increases from 5 to 20 D, where D is the needle diameter, the solution from each needle encounters 3.5 times faster, and 4.22 times more solution was accumulated. At the same time, the effective spreading area was continuously increased from 54.2 to 177.8 mm2 and RCS gradient decreases from 0.087 to 0.037, due to the overlapping effect of the spreading solution from neighboring needles. Finally, based on the experimental results, an optimal design criterion of needle array for effective drug delivery was proposed. The present results would be helpful in the design of multi-needle injection devices and eventually offer advantage to patients with effective drug delivery.

Keywords

Drug injection Multi-needle injection X-ray imaging Diffusion 

Notes

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korea government (MSIP) (No. 2017R1A2B3005415).

Competing financial interests

The authors declare no competing financial interests.

Author contributions

HP, HK and SJL proposed the study. HP and HK performed the experiment and they processed the captured images and analyzed the experimental data. All authors discussed the results and participated in completing the manuscript.

References

  1. 1.
    Berteau, C., O. Filipe-Santos, T. Wang, H. E. Rojas, C. Granger, and F. Schwarzenbach. Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance. Med. Dev. 8:473, 2015.Google Scholar
  2. 2.
    Cemeroglu, A., A. Can, A. Davis, O. Cemeroglu, L. Kleis, M. Daniel, J. Bustraan, and T. Koehler. Fear of needles in children with type 1 diabetes mellitus on multiple daily injections and continuous subcutaneous insulin infusion. Endoc. Pract. 21:46–53, 2014.CrossRefGoogle Scholar
  3. 3.
    Comley, K., and N. Fleck. The mechanical response of porcine adipose tissue. ASME J. Biomech. Eng. 1:1–30, 2009.Google Scholar
  4. 4.
    Comley, K., and N. Fleck. Deep penetration and liquid injection into adipose tissue. J. Mech. Mater. Struct. 6:127–140, 2011.CrossRefGoogle Scholar
  5. 5.
    Cullity, B. D. Elements of X-ray Diffraction. Pearson: New Jearsey, 2001.Google Scholar
  6. 6.
    Dev, S. B., D. Dhar, and W. Krassowska. Electric field of a six-needle array electrode used in drug and DNA delivery in vivo: analytical versus numerical solution. IEEE Trans. Biomed. Eng. 50:1296–1300, 2003.CrossRefGoogle Scholar
  7. 7.
    Douglas, W. R. Of pigs and men and research. Space Life Sci. 3:226–234, 1972.Google Scholar
  8. 8.
    Frid, A., L. Hirsch, R. Gaspar, D. Hicks, G. Kreugel, J. Liersch, C. Letondeur, J.-P. Sauvanet, N. Tubiana-Rufi, and K. Strauss. New injection recommendations for patients with diabetes. Diabet. Metab. 36:S3–S18, 2010.CrossRefGoogle Scholar
  9. 9.
    Gill, H. S., D. D. Denson, B. A. Burris, and M. R. Prausnitz. Effect of microneedle design on pain in human subjects. Clinic. J. Pain 24:585, 2008.CrossRefGoogle Scholar
  10. 10.
    Gin, H., and H. Hanaire-Broutin. Reproducibility and variability in the action of injected insulin. Diabet. Metab. 31:7–13, 2005.CrossRefGoogle Scholar
  11. 11.
    Gupta, S. Double needle technique: an alternative method for performing difficult sacroiliac joint injections. Pain Phys. 14:281–284, 2011.Google Scholar
  12. 12.
    Hamilton, J. G. Needle phobia: a neglected diagnosis. J. Fam. Prac. 41:169–176, 1995.Google Scholar
  13. 13.
    Hofman, P. L., J. G. B. Derraik, T. E. Pinto, S. Tregurtha, A. Faherty, J. M. Peart, P. L. Drury, E. Robinson, R. Tehranchi, and M. Donsmark. Defining the ideal injection techniques when using 5-mm needles in children and adults. Diabet. Care 33:1940–1944, 2010.CrossRefGoogle Scholar
  14. 14.
    Jin, C. Y., M. H. Han, S. S. Lee, and Y. H. Choi. Mass producible and biocompatible microneedle patch and functional verification of its usefulness for transdermal drug delivery. Biomed. Microdev. 11:1195, 2009.CrossRefGoogle Scholar
  15. 15.
    Jockel, J. P. L., P. Roebrock, O. A. Shergold, and C. Huwiler. Insulin depot formation in subcutaneous tissue. J. Diabet. Sci. Tech. 7:227–237, 2013.CrossRefGoogle Scholar
  16. 16.
    Johnson, O. L., J. L. Cleland, H. J. Lee, M. Charnis, E. Duenas, W. Jaworowicz, D. Shepard, A. Shahzamani, A. J. Jones, and S. D. Putney. A month-long effect from a single injection of microencapsulated human growth hormone. Nat. Medic. 2:795–799, 1996.CrossRefGoogle Scholar
  17. 17.
    Jung, S. Y., S. Lim, and S. J. Lee. Investigation of water seepage through porous media using X-ray imaging technique. J. Hydrol. 452:83–89, 2012.CrossRefGoogle Scholar
  18. 18.
    Kim, S., M. Dangol, G. Kang, S. F. Lahiji, H. Yang, M. Jang, Y. Ma, C. Li, S. G. Lee, and C. H. Kim. Enhanced transdermal delivery by combined application of dissolving microneedle patch on serum-treated skin. Mol. Pharm. 14:2024–2031, 2017.CrossRefGoogle Scholar
  19. 19.
    Kim, H., H. Park, and S. J. Lee. Effective method for drug injection into subcutaneous tissue. Sci. Rep. 7:9613, 2017.CrossRefGoogle Scholar
  20. 20.
    Lee, J. W., S. O. Choi, E. I. Felner, and M. R. Prausnitz. Dissolving microneedle patch for transdermal delivery of human growth hormone. Small 7:531–539, 2011.CrossRefGoogle Scholar
  21. 21.
    Lee, I., W. M. Lin, J. C. Shu, S. W. Tsai, C. H. Chen, and M. T. Tsai. Formulation of two-layer dissolving polymeric microneedle patches for insulin transdermal delivery in diabetic mice. J. Biomed. Mater. Res. Part A 105:84–93, 2017.CrossRefGoogle Scholar
  22. 22.
    Nakano, A., A. Matsumori, S. Kawamoto, H. Tahara, E. Yamato, S. Sasayama, and J.-I. Miyazaki. Cytokine gene therapy for myocarditis by in vivo electroporation. Hum. Gene Ther. 12:1289–1297, 2001.CrossRefGoogle Scholar
  23. 23.
    Onodera, S., S. Ohshima, H. Tohyama, K. Yasuda, J. Nishihira, Y. Iwakura, I. Matsuda, A. Minami, and Y. Koyama. A novel DNA vaccine targeting macrophage migration inhibitory factor protects joints from inflammation and destruction in murine models of arthritis. Arthritis Rheum. 56:521–530, 2007.CrossRefGoogle Scholar
  24. 24.
    Prausnitz, M. R. Engineering microneedle patches for vaccination and drug delivery to skin. Annu. Rev. Chem. Biomol. Eng. 8:177–200, 2017.CrossRefGoogle Scholar
  25. 25.
    Seong, K.-Y., M. S. Seo, D. Y. Hwang, E. D. O’Cearbhaill, S. Sreenan, J. M. Karp, and S. Y. Yang. A self-adherent, bullet-shaped microneedle patch for controlled transdermal delivery of insulin. J. Control. Release 265:48–56, 2017.CrossRefGoogle Scholar
  26. 26.
    Thomsen, M., M. Poulsen, M. Bech, A. Velroyen, J. Herzen, F. Beckmann, R. Feidenhans, and F. Pfeiffer. Visualization of subcutaneous insulin injections by X-ray computed tomography. Phys. Med. Biol. 57:7191, 2012.CrossRefGoogle Scholar
  27. 27.
    Williams, J., L. Fox-Leyva, C. Christensen, D. Fisher, E. Schlicting, M. Snowball, S. Negus, J. Mayers, R. Koller, and R. Stout. Hepatitis A vaccine administration: comparison between jet-injector and needle injection. Vaccine 18:1939–1943, 2000.CrossRefGoogle Scholar

Copyright information

© Biomedical Engineering Society 2018

Authors and Affiliations

  1. 1.Center for Biofluid and Biomimic Research, Pohang University of Science and Technology (POSTECH)PohangSouth Korea
  2. 2.Department of Mechanical EngineeringPohang University of Science and Technology (POSTECH)PohangSouth Korea

Personalised recommendations