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Transdermal Delivery of Interferon Alpha-2B using Microporation and Iontophoresis in Hairless Rats

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Abstract

Purpose

To demonstrate transdermal delivery of interferon alpha-2b (IFNα2b) in hairless rats through aqueous microchannels (micropores) created in the skin and enhanced by iontophoresis.

Materials and Methods

The Altea Therapeutics PassPort™ System was configured to form an array of micropores (2.0 cm2; 72 micropores/cm2) on the rat abdomen. The transdermal patch (Iomed TransQ1-GS-hydrogel) was saturated with an IFNα2b solution (600 μg/ml) and applied for 4 h. Delivery was evaluated with and without cathodic iontophoresis (0.1 mA/cm2). Intravenous delivery (0.4 μg/100 g body weight) was performed to support pharmacokinetic calculations.

Results

IFNα2b was not delivered through intact skin by itself (passive delivery) or during iontophoresis. However, passive delivery through micropores was achieved in vivo in rats. A dose of 397 ± 67 ng was delivered over 6 h, with steady state serum concentrations reaching a plateau at 1 h post-patch application. These levels dropped rapidly after patch removal, and returned to baseline within 2 h of patch removal. Iontophoresis-enhanced delivery through micropores resulted in a two-fold increase in the dose delivered (722 ± 169 ng) in the hairless rat.

Conclusions

In vivo delivery of IFNα2b was demonstrated through micropores created in the outer layer of the skin. Iontophoresis enhanced delivery through microporated skin in hairless rats.

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Acknowledgements

The authors would like to acknowledge Rajkumar Conjeevaram, Aniket Badkar and Ayyappa Chaturvedula for their help with animal handling and with the WinNonlin® software. We want to thank Pharsight Corporation (Mountain view, CA) for the academic license to WinNonlin® software.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, Georgia, 30341, USA

    Advait V. Badkar & Ajay K. Banga

  2. Altea Therapeutics, Tucker, Georgia, 30084, USA

    Alan M. Smith & Jonathan A. Eppstein

  3. Pharmaceutical R&D, Global Biologics, Pfizer Inc., St. Louis, Missouri, 63017, USA

    Advait V. Badkar

Authors
  1. Advait V. Badkar
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  2. Alan M. Smith
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  4. Ajay K. Banga
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Correspondence to Ajay K. Banga.

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Badkar, A.V., Smith, A.M., Eppstein, J.A. et al. Transdermal Delivery of Interferon Alpha-2B using Microporation and Iontophoresis in Hairless Rats. Pharm Res 24, 1389–1395 (2007). https://doi.org/10.1007/s11095-007-9308-2

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  • DOI: https://doi.org/10.1007/s11095-007-9308-2

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