title: A microneedle-based method for the characterization of diffusion in skin tissue using doxorubicin as a model drug.
abstract: Hollow microneedles can overcome the stratum corneum (SC) barrier and deposit a compound directly into the viable epidermis or the dermis, unlike adhesive patches that rely on drug diffusion across the SC. The traditional one-dimensional methods used to study the diffusivity of drugs across the skin layers are not very accurate for hollow microneedles, since the ejection of compounds out of microneedle lumens resembles a point-source spreading in all directions and is highly dependent on injection depth. This paper presents a technique that is useful for studying drug injection using hollow microneedles at various depths below the SC. This technique uses confocal microscopy to image the distribution of a fluorescent compound in the skin after injection. The fluorescence distribution in the skin is observed over time and applied to a spherical Gaussian diffusion model for limited source diffusion to determine the diffusion coefficient of the compound in the skin. Applied to freshly excised pig skin, the diffusion coefficient for the anti-cancer drug doxorubicin was measured as 4.61 × 10(-9) cm(2)/s, while the diffusion coefficient in previously refrigerated or frozen pig skin was 1.31 × 10(-8) cm(2)/s and 4.21 × 10(-8) cm(2)/s, respectively. Our data suggests that skin storage conditions can substantially alter the diffusion of drugs. The use of refrigerated and, even more so, previously frozen skin should be avoided for quantitative transdermal drug delivery studies.
authors.affiliation: Department of Electrical and Computer Engineering, The University of British Columbia, 5500 - 2332 Main Mall, Vancouver, BC, Canada, V6T 1Z4.
authors.forename: Iman
authors.initials: I
authors.lastname: Mansoor
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lai
authors.forename: Sahan
authors.initials: S
authors.lastname: Ranamukhaarachchi
authors.forename: Veronika
authors.initials: V
authors.lastname: Schmitt
authors.forename: Dana
authors.initials: D
authors.lastname: Lambert
authors.forename: Jan
authors.initials: J
authors.lastname: Dutz
authors.forename: Urs O
authors.initials: UO
authors.lastname: Häfeli
authors.forename: Boris
authors.initials: B
authors.lastname: Stoeber
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008845:Microinjections / Q000295:instrumentation*; D018613:Microscopy, Confocal / Q000379:methods*; D008856:Microscopy, Fluorescence / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods; D009339:Needles; D012867:Skin / Q000737:chemistry*; D012869:Skin Absorption; D013552:Swine; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin