Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats
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Feasibility study of two-layered dissolving microneedles for percutaneous delivery of peptide/proteins using recombinant human growth hormone (rhGH) and desmopressin (DDAVP).
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.
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.
Results suggest that the two-layered dissolving microneedles are useful as an immediate-release transdermal DDS for peptide/protein drugs.
KEY WORDSbioavailability desmopressin (DDAVP) dissolving microneedles recombinant human growth hormone (rhGH) transdermal delivery
- 1.Walsh G. Biopharmaceuticals. West Sussex: Wiley; 2003.Google Scholar
- 34.Takada K. Microfabrication derived DDS: From batch to individual production. Drug Discov Ther. 2008;2:140–55.Google Scholar
- 39.Gibaldi M, Perrier D. Pharmacokinetics. New York: Marcel Dekker; 2006.Google Scholar
- 40.Ito Y, Ise A, Sugioka N, Takada K. Molecular weight dependence on bioavailabity of FITC-dextran after administration of self-dissolving micropile to rat skin. Drug Dev Ind Pharm. in press (2010).Google Scholar
- 42.Bauer J, Bahmer AF, Worl J, Neuhuber W, Schuler G, Fartasch M. A strikingly constant ration exists between Langerhans cells and other epidermal cells in human skin. A stereologic study using the optical dissector method and the confocal laser scanning microscope. J Invest Dermatol. 2001;116:313–8.CrossRefPubMedGoogle Scholar
- 45.Ito Y, Hasegawa R, Fukushima K, Sugioka N, Takada K. Self-dissolving micropile array chip as percutaneous delivery system of protein drug. Biol Pharm Bull. in press (2010).Google Scholar
- 59.Steiner IM, Kaehler ST, Sauermann R, Rinosl H, Muller M, Joukhadar C. Plasma pharmacokinetics of desmopressin following sublingual administration: an exploratory dose-escalation study in healthy male volunteers. Int J Clin Pharm Ther. 2006;44:172–9.Google Scholar
- 61.de Jager MW, Ponec M, Bouwstra JA. The lipid organization in stratum corneum and model systems based on ceramides. In: Touitou E, Barry BW, editors. Enhancement in drug delivery. London: CRC; 2007. p. 217–32.Google Scholar