Pharmaceutical Research

, Volume 28, Issue 1, pp 7–21

Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats

  • Keizo Fukushima
  • Ayaka Ise
  • Hiromi Morita
  • Ryo Hasegawa
  • Yukako Ito
  • Nobuyuki Sugioka
  • Kanji Takada
Research Paper

DOI: 10.1007/s11095-010-0097-7

Cite this article as:
Fukushima, K., Ise, A., Morita, H. et al. Pharm Res (2011) 28: 7. doi:10.1007/s11095-010-0097-7

ABSTRACT

Purpose

Feasibility study of two-layered dissolving microneedles for percutaneous delivery of peptide/proteins using recombinant human growth hormone (rhGH) and desmopressin (DDAVP).

Methods

Two-layered dissolving microneedles were administered percutaneously to the rat skin. Plasma rhGH and DDAVP concentrations were measured by EIA and LC/MS/MS. In vivo dissolution and diffusion rates of drugs in the skin were studied using tracer dyes, lissamine green B (LG) for rhGH and evans blue (EB) for DDAVP. Diffusion of drugs vertically into the skin was studied using FITC-dextran (MW = 20 kDa)-loaded dissolving microneedles. Stability experiments were performed at −80°C and 4°C.

Results

The absorption half-lives, t1/2a, of rhGH and DDAVP from dissolving microneedles were 23.7 ± 4.3–28.9 ± 5.2 and 14.4 ± 2.9–14.1 ± 1.1 min; the extents of bioavailability were 72.8 ± 4.2–89.9 ± 10.0% and 90.0 ± 15.4–93.1 ± 10.3%, respectively. LG and EB disappeared from the administered site within 2 h and 3 h after administration. Five green fluorescein spots were detected at 15 s and enlarged transversally at 30 s. FITC-dextran was delivered into the microcapillaries at 5 min and 10 min. The rhGH and DDAVP were stable in dissolving microneedles for one month at −80°C and 4°C.

Conclusions

Results suggest that the two-layered dissolving microneedles are useful as an immediate-release transdermal DDS for peptide/protein drugs.

KEY WORDS

bioavailabilitydesmopressin (DDAVP)dissolving microneedlesrecombinant human growth hormone (rhGH)transdermal delivery

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Keizo Fukushima
    • 1
  • Ayaka Ise
    • 1
  • Hiromi Morita
    • 1
  • Ryo Hasegawa
    • 1
  • Yukako Ito
    • 1
  • Nobuyuki Sugioka
    • 1
  • Kanji Takada
    • 1
  1. 1.Department of PharmacokineticsKyoto Pharmaceutical UniversityKyotoJapan