caa a22 4500 445311673 CHVBK 20180317142632.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s11095-010-0097-7 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0097-7 Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats [Elektronische Daten] [Keizo Fukushima, Ayaka Ise, Hiromi Morita, Ryo Hasegawa, Yukako Ito, Nobuyuki Sugioka, Kanji Takada] 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 = 20kDa)-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 ± 1.1min; 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 2h and 3h after administration. Five green fluorescein spots were detected at 15s and enlarged transversally at 30s. FITC-dextran was delivered into the microcapillaries at 5min and 10min. 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. Springer Science+Business Media, LLC, 2010 bioavailability nationallicence desmopressin (DDAVP) nationallicence dissolving microneedles nationallicence recombinant human growth hormone (rhGH) nationallicence transdermal delivery nationallicence Fukushima Keizo Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut Ise Ayaka Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut Morita Hiromi Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut Hasegawa Ryo Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut Ito Yukako Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut Sugioka Nobuyuki Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut Takada Kanji Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/1(2011-01-01), 7-21 0724-8741 28:1<7 2011 28 11095 https://doi.org/10.1007/s11095-010-0097-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0097-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fukushima Keizo Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut NATIONALLICENCE 700 1- Ise Ayaka Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut NATIONALLICENCE 700 1- Morita Hiromi Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut NATIONALLICENCE 700 1- Hasegawa Ryo Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut NATIONALLICENCE 700 1- Ito Yukako Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut NATIONALLICENCE 700 1- Sugioka Nobuyuki Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut NATIONALLICENCE 700 1- Takada Kanji Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 607-8412, Kyoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/1(2011-01-01), 7-21 0724-8741 28:1<7 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer