Enhancemen of skin permeation of high molecular compounds by a.doc

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Enhancemen of skin permeation of high molecular compounds by a.doc

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Enhancemen of skin permeation of high molecular compounds by a

Enhancement of skin permeation of high molecular compounds by a combination of microneedle pretreatment and iontophoresis Xue-Ming Wu, Hiroaki Todo, Kenji Sugibayashi ? Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan Received 21 October 2006; accepted 14 December 2006 Available online 23 December 2006 Abstract A combination of microneedle pretreatment and iontophoresis was evaluated for the potential to increase skin permeation of drugs. Two model compounds with low and high molecular D2O and fluorescein isothiocyanate (FITC)-dextrans (FD-4, FD-10, FD-40, FD-70 and FD-2000; average molecular weight of 3.8, 10.1, 39.0, 71.2 and 200.0 kDa), respectively, were used and the effect of microneedle pretreatment and iontophoresis on their in vitro permeability was evaluated using excised hairless rat skin with a 2-chamber diffusion cell. Convective solvent flow through the skin was measured using a set of calibrated capillaries attached to the diffusion cell. The following results were obtained: (1) convective solvent flow (electroosmosis) during iontophoresis through microneedle-pretreated skin, 2.62?0.32 μL/cm2/h, was almost the same as through intact skin, 2.71±0.25 μL/cm2/h, and (2) the combination of microneedle pretreatment and subsequent iontophoresis significantly enhanced FD flux compared with microneedle pretreatment alone or iontophoresis alone, whereas no synergistic effect was found on the flux of D2O. These results suggest that the combination of iontophoresis with microneedle pretreatment may be a useful means to increase skin permeation of high molecular compounds. ? 2007 Elsevier B.V. All rights reserved. Keywords: Microneedle; Iontophoresis; Electroosmosis; High molecular compounds; FITC-dextrans 1. Introduction In order to overcome the formidable barrier of the stratum corneum to drug permeation, several skin penetration-enhancing strategies have been developed by physical means such as iontophoresis