title: Enhancement of skin permeation of high molecular compounds by a combination of microneedle pretreatment and iontophoresis.
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 D(2)O 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 microL/cm(2)/h, was almost the same as through intact skin, 2.71+/-0.25 microL/cm(2)/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 D(2)O. These results suggest that the combination of iontophoresis with microneedle pretreatment may be a useful means to increase skin permeation of high molecular compounds.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Wu
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Todo
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugibayashi
mesh_terms: D026881:Acupuncture / Q000295:instrumentation*; D000279:Administration, Cutaneous; D000818:Animals; D017666:Deuterium Oxide / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D015194:Diffusion Chambers, Culture; D053841:Electroosmosis; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D007478:Iontophoresis; D008297:Male; D008954:Models, Biological; D008970:Molecular Weight; D009339:Needles; D009924:Organ Culture Techniques; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains; D012869:Skin Absorption; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
chemical_list: D003911:Dextrans; D012997:Solvents; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D017666:Deuterium Oxide