Transdermal Delivery of Interferon Alpha-2B using Microporation and Iontophoresis in Hairless Rats |
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Authors: | Advait V. Badkar Alan M. Smith Jonathan A. Eppstein Ajay K. Banga |
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Affiliation: | (1) Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Mercer University, Atlanta, Georgia 30341, USA;(2) Altea Therapeutics, Tucker, Georgia 30084, USA;(3) Pharmaceutical R&D, Global Biologics, Pfizer Inc., St. Louis, Missouri 63017, USA |
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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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Keywords: | interferon alpha iontophoresis microporation protein delivery transdermal delivery |
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