Self-dissolving micropile array tips for percutaneous administration of insulin

  • Yukako Ito
  • Takenao Yamazaki
  • Nobuyuki Sugioka
  • Kanji Takada
Article

Abstract

Two kinds of insulin were loaded into self-dissolving micropile array tip (following tip). Fully-loaded tip (f-tip) and partially-loaded tip (p-tip) were prepared using chondroitin sulfate for the percutaneous administration of insulin. One hundred micropiles were constructed on a 1.0 × 1.0 cm tip. The mean length of the micropile in a tip were 483.4 ± 4.7 μm for the f-tip and 492.6 ± 2.4 μm for the p-tip. The insulin content of the p-tip was 28.5% of that of the f-tip. The pharmacological efficiency of insulin loaded tip was evaluated in rat experiments by measuring their hypoglycemic effects. The maximum hypoglycemic effect of insulin was observed at 1.7 ± 0.2 h for the f-tip and 1.5 ± 0.2 h for the p-tip. Good dose-dependency was observed for the plasma glucose level vs. time curves. These results suggest the usefulness of p-tip as a percutaneous DDS of insulin.

Notes

Acknowledgments

This study was supported by a strategic fund of MEXT (Ministry of Education, Culture, Sports, Science and Technology, MEXT) from 2008 to 2010 for establishing research foundations in Japanese private universities. This study was also partially supported by the Uehara Memorial Foundation.

References

  1. 1.
    Henry S, McAllister DV, Allen MG, Prausnitz MR. Microfabricated micropiles: a novel approach to transdermal drug delivery. J Pharm Sci. 1998;87:922–5.CrossRefPubMedGoogle Scholar
  2. 2.
    Teo MA, Shearwood C, Ng KC, Lu J, Moochhala S. In vitro and in vivo characterization of MEMS micropiles. Biomed Microdev. 2005;7:47–52.CrossRefGoogle Scholar
  3. 3.
    Park JH, Allen MG, Prausnitz MR. Polymer micropiles for control1ed-release drug delivery. Pharm Res. 2006;23:1008–19.CrossRefPubMedGoogle Scholar
  4. 4.
    Davis SP, Martanto W, Allen MG, Prausnitz MR. Hollow metal micropiles for insulin delivery to diabetic rats. IEEE Trams Biomed Eng. 2005;52:909–15.CrossRefGoogle Scholar
  5. 5.
    McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci USA. 2003;100:13755–60.CrossRefPubMedADSGoogle Scholar
  6. 6.
    Prausnitz MR. Micropiles for transdermal drug delivery. Adv Drug Deliv Rev. 2004;56:581–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Birchall JC. Stratum corneum bypassed or removed. In: Touitou E, Barry BW, editors. Enhancement in drug delivery. New York: CRC Press; 2007. p. 337–51.Google Scholar
  8. 8.
    Wermeling DP, Banks SL, Hudson DA, Gill HS, Gupta J, Prausnitz MR, et al. Micropiles permit transdermal delivery of a skin-impermeant medication to humans. Proc Natl Acad Sci USA. 2008;105:2058–63.CrossRefPubMedADSGoogle Scholar
  9. 9.
    Kolli CS, Banga AK. Characterization of solid maltose microneedles and their use for transdermal delivery. Pharm Res. 2008;25:104–13.CrossRefPubMedGoogle Scholar
  10. 10.
    Ravi S, Khiang PK, Darwis Y, Murthy BK, Rai STR. Development and validation of an HPLC-UV method for the determination of insulin in rat plasma: application to pharmacokinetic study. Chromatography. 2007;66:805–9.CrossRefGoogle Scholar
  11. 11.
    Monteiro-Riviere NA, Bristol DG, Manning TO, Rogers RA, Riviere JE. Interspecies and interregional analysis of the comparative histologic thickness and laser Doppler blood flow measurements at five cutaneous sites in nine species. J Inv Dermatol. 1990;95:582–6.CrossRefGoogle Scholar
  12. 12.
    Bauer J, Bahmer FA, 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 Inv Dermatol. 2001;116:313–8.CrossRefGoogle Scholar
  13. 13.
    Caspers PJ, Lucassen GW, Bruining HA, Puppels GJ. Automated depth-scanning confocal Raman microspectrometer for rapid in vivo determination of water concentration profiles in human skin. J Raman Spectrosc. 2000;31:813–8.CrossRefADSGoogle Scholar
  14. 14.
    Turncliff RZ, Dunbar JL, Dong Q, Silverman BL, Ehrich EW, Dilzer SC, et al. Pharmacokinetics of long-acting naltrexone in subjects with mild to moderate hepatic impairment. J Clin Pharmacol. 2005;45:1259–67.CrossRefPubMedGoogle Scholar
  15. 15.
    Gill HS, Prausnitz MR. Coated micropiles for transdermal delivery. J Control Rel. 2007;117:227–37.CrossRefGoogle Scholar
  16. 16.
    Gill HS, Prausnitz MR. Coating formulations for micropiles. Pharm Res. 2007;24:1369–80.CrossRefPubMedGoogle Scholar
  17. 17.
    Cormier M, Johnson B, Ameri M, Nyam K, Libiran L, Zhang D, et al. Transdermal delivery of desmopressin using a coated microneedle array patch system. J Control Rel. 2004;97:503–11.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Yukako Ito
    • 1
  • Takenao Yamazaki
    • 1
  • Nobuyuki Sugioka
    • 1
  • Kanji Takada
    • 1
  1. 1.Department of PharmacokineticsKyoto Pharmaceutical UniversityKyotoJapan

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