Advertisement

BioChip Journal

, Volume 12, Issue 4, pp 309–316 | Cite as

Clinical Evaluation of a Low-pain Long Microneedle for Subcutaneous Insulin Injection

  • Ghunil Lee
  • Yonghao Ma
  • Yong-ho Lee
  • Hyungil JungEmail author
Original Article
  • 17 Downloads

Abstract

Microneedles (MNs) are being developed to overcome the limitations of the conventional hypodermic needle, e.g. the injection pain. In this study, we conducted an analysis of clinical pain and bleeding at the site of MN insertion and evaluated the insulin pharmacodynamic profile compared with parameters obtained with a conventional pen needle. MN insertion into the skin of 25 healthy adults or 15 patients with type 2 diabetes (T2D) revealed significantly less pain relative to a conventional hypodermic pen needle, thus reducing pain scores from 2.1±1.9 to 1.3±1.4 (mean±standard deviation [SD]). Besides, no bleeding was observed when the MN was used. In the insulin pharmacodynamic assay, no significant differences were observed in the blood glucose-lowering effect between the pen needle and MN. Based on these results, the MN is expected to be a good substitute for conventional hypodermic pen needles and improve the quality of life of patients by significantly reducing the pain associated with insulin treatment.

Keywords

Microneedle Insulin Subcutaneous injection Pain Bleeding Pharmacodynamic profile 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fraser, R. Metabolic disorders in diabetes. Br. Med. J. 4, 591–596 (1972).CrossRefGoogle Scholar
  2. 2.
    Nathan, D.M. et al. The effect of intensive treatment of diabetes on the development and progression of longterm complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 329, 977–986 (1993).CrossRefGoogle Scholar
  3. 3.
    Nathan, D.M. et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N. Engl. J. Med. 353, 2643–2653 (2005).CrossRefGoogle Scholar
  4. 4.
    Hameed, I. et al. Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition. World J. Diabetes 6, 598–612 (2015).CrossRefGoogle Scholar
  5. 5.
    Thrasher, J. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. Am. J. Cardiol. 120, S4-S16 (2017).Google Scholar
  6. 6.
    CADTH Therapeutic Reviews. in Third-line Drugs for Type 2 Diabetes-Project Protocol (Canadian Agency for Drugs and Technologies in Health. Copyright (c) 2017 Canadian Agency for Drugs and Technologies in Health., Ottawa (ON), 2017).Google Scholar
  7. 7.
    Humphrey, M.J. The Oral Bioavailability of Peptides and Related Drugs. in Delivery Systems for Peptide Drugs (eds. Davis, S.S., Illum, L. & Tomlinson, E.) 139–151 (Springer US, Boston, MA, 1986).Google Scholar
  8. 8.
    Shaji, J. & Patole, V. Protein and Peptide Drug Delivery: Oral Approaches. Indian J. Pharm. Sci. 70, 269–277 (2008).CrossRefGoogle Scholar
  9. 9.
    Rubin, R.R., Peyrot, M., Kruger, D.F. & Travis, L.B. Barriers to insulin injection therapy: patient and health care provider perspectives. Diabetes Educ. 35, 1014–1022 (2009).CrossRefGoogle Scholar
  10. 10.
    Aronson, R. The Role of Comfort and Discomfort in Insulin Therapy. Diabetes Technol. Ther. 14, 741–747 (2012).CrossRefGoogle Scholar
  11. 11.
    Oleck, J., Kassam, S. & Goldman, J.D. Commentary: Why Was Inhaled Insulin a Failure in the Market? Diabetes Spectr. 29, 180–184 (2016).CrossRefGoogle Scholar
  12. 12.
    Kling, J. Inhaled insulin’s last gasp? Nat. Biotechnol. 26, 479–480 (2008).Google Scholar
  13. 13.
    Mohanty, R.R. & Das, S. Inhaled Insulin-Current Di rection of Insulin Research. J. Clin. Diagn. Res. 11, OE01-OE02 (2017).Google Scholar
  14. 14.
    Gill, H.S., Denson, D.D., Burris, B.A. & Prausnitz, M.R. Effect of microneedle design on pain in human subjects. Clin. J. Pain 24, 585–594 (2008).CrossRefGoogle Scholar
  15. 15.
    Martanto, W. et al. Transdermal delivery of insulin using microneedles in vivo. Pharm. Res. 21, 947–952 (2004).CrossRefGoogle Scholar
  16. 16.
    Gill, H.S. & Prausnitz, M.R. Coated microneedles for transdermal delivery. J. Control. Release 117, 227–237 (2007).CrossRefGoogle Scholar
  17. 17.
    Martin, C.J., Allender, C.J., Brain, K.R., Morrissey, A. & Birchall, J.C. Low temperature fabrication of biodegradable sugar glass microneedles for transdermal drug delivery applications. J. Control. Release 158, 93–101 (2012).CrossRefGoogle Scholar
  18. 18.
    Gill, H.S. & Prausnitz, M.R. Pocketed Microneedles for Drug Delivery to the Skin. J. Phys. Chem. Solids 69, 1537–1541 (2008).CrossRefGoogle Scholar
  19. 19.
    Gupta, J., Felner, E.I. & Prausnitz, M.R. Rapid pharmacokinetics of intradermal insulin administered using microneedles in type 1 diabetes subjects. Diabetes Technol. Ther. 13, 451–456 (2011).CrossRefGoogle Scholar
  20. 20.
    Pettis, R.J. et al. Intradermal microneedle delivery of insulin lispro achieves faster insulin absorption and insulin action than subcutaneous injection. Diabetes Technol. Ther. 13, 435–442 (2011).CrossRefGoogle Scholar
  21. 21.
    McAllister, D.V. et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: Fabrication methods and transport studies. Proc. Natl. Acad. Sci. USA 100, 13755–13760 (2003).CrossRefGoogle Scholar
  22. 22.
    Akkus, O., Oguz, A., Uzunlulu, M. & Kizilgul, M. Evaluation of skin and subcutaneous adipose tissue thickness for optimal insulin injection. J. Diabetes Metab. 3, 2 (2012).CrossRefGoogle Scholar
  23. 23.
    Norman, J.J., Brown, M.R., Raviele, N.A., Prausnitz, M.R. & Felner, E.I. Faster pharmacokinetics and increased patient acceptance of intradermal insulin delivery using a single hollow microneedle in children and adolescents with type 1 diabetes. Pediatr Diabetes 14, 459–465 (2013).CrossRefGoogle Scholar
  24. 24.
    Gupta, J., Felner, E.I. & Prausnitz, M.R. Minimally invasive insulin delivery in subjects with type 1 diabetes using hollow microneedles. Diabetes Technol. Ther. 11, 329–337 (2009).CrossRefGoogle Scholar
  25. 25.
    Li, C.G. et al. A Novel Ultrafine Needle (UN) for Innocuous and Efficient Subcutaneous Insulin Delivery. Advanced Functional Materials 27, (2017).CrossRefGoogle Scholar
  26. 26.
    Pettis, R.J. et al. Microneedle-based intradermal versus subcutaneous administration of regular human insulin or insulin lispro: pharmacokinetics and postprandial glycemic excursions in patients with type 1 diabetes. Diabetes Technol. Ther. 13, 443–450 (2011).CrossRefGoogle Scholar
  27. 27.
    Kochba, E., Levin, Y., Raz, I. & Cahn, A. Improved Insulin Pharmacokinetics Using a Novel Microneedle Device for Intradermal Delivery in Patients with Type 2 Diabetes. Diabetes Technol. Ther. 18, 525–531 (2016).CrossRefGoogle Scholar
  28. 28.
    Lee, C.Y., Lee, K., You, Y.S., Lee, S.H. & Jung, H. Tower microneedle via reverse drawing lithography for innocuous intravitreal drug delivery. Adv. Healthc. Mater. 2, 812–816 (2013).CrossRefGoogle Scholar
  29. 29.
    McKay, M., Compion, G. & Lytzen, L. A comparison of insulin injection needles on patients’ perceptions of pain, handling, and acceptability: A randomized, open-label, crossover study in subjects with diabetes. Diabetes Technol. Ther. 11, 195–201 (2009)CrossRefGoogle Scholar
  30. 30.
    Miwa, T. et al. Comparison of the effects of a new 32-gauge x 4-mm pen needle and a 32-gauge x 6-mm pen needle on glycemic control, safety, and patient ratings in Japanese adults with diabetes. Diabetes Technol. Ther. 14, 1084–1090 (2012).CrossRefGoogle Scholar
  31. 31.
    Lee, K., Lee, H.C., Lee, D.S. & Jung, H. Drawing lithography: three-dimensional fabrication of an ultrahigh-aspect-ratio microneedle. Adv. Mater. 22, 483–486 (2010).CrossRefGoogle Scholar

Copyright information

© The Korean BioChip Society and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biomaterials Science and EngineeringYonsei UniversitySeoulRepublic of Korea
  2. 2.Department of BiotechnologyYonsei UniversitySeoulRepublic of Korea
  3. 3.Department of Internal MedicineYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Juvic Inc.SeoulRepublic of Korea

Personalised recommendations