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

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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, t 1/2a, 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.

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ACKNOWLEDGMENTS

This study was supported by a strategic fund of MEXT (Ministry of Education, Culture, Sports, Science and Technology, MEXT) from 2008 to 2013 for establishing research foundation in private universities of Japan.

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  1. Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8412, Japan

    Keizo Fukushima, Ayaka Ise, Hiromi Morita, Ryo Hasegawa, Yukako Ito, Nobuyuki Sugioka & Kanji Takada

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  1. Keizo Fukushima
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  2. Ayaka Ise
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  3. Hiromi Morita
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  4. Ryo Hasegawa
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  5. Yukako Ito
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  6. Nobuyuki Sugioka
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  7. Kanji Takada
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Correspondence to Keizo Fukushima.

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Fukushima, K., Ise, A., Morita, H. et al. Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats. Pharm Res 28, 7–21 (2011). https://doi.org/10.1007/s11095-010-0097-7

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