caa a22 4500 605479712 CHVBK 20210128100411.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10544-015-9967-4 doi (NATIONALLICENCE)springer-10.1007/s10544-015-9967-4 A microneedle-based method for the characterization of diffusion in skin tissue using doxorubicin as a model drug [Elektronische Daten] [Iman Mansoor, Jacqueline Lai, Sahan Ranamukhaarachchi, Veronika Schmitt, Dana Lambert, Jan Dutz, Urs Häfeli, Boris Stoeber] 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 × 10−9cm2/s, while the diffusion coefficient in previously refrigerated or frozen pig skin was 1.31 × 10−8cm2/s and 4.21 × 10-8cm2/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. Springer Science+Business Media New York, 2015 Hollow microneedles nationallicence Transdermal drug delivery nationallicence Doxorubicin nationallicence Confocal microscopy nationallicence Diffusion nationallicence Mansoor Iman Department of Electrical and Computer Engineering, The University of British Columbia, 5500 - 2332 Main Mall, V6T 1Z4, Vancouver, BC, Canada aut Lai Jacqueline Department of Dermatology and Skin Science, The University of British Columbia, 835 West 10th Avenue, V5Z 4E8, Vancouver, BC, Canada aut Ranamukhaarachchi Sahan Department of Electrical and Computer Engineering, The University of British Columbia, 5500 - 2332 Main Mall, V6T 1Z4, Vancouver, BC, Canada aut Schmitt Veronika Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, V6T 1Z3, Vancouver, BC, Canada aut Lambert Dana Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, V6T 1Z3, Vancouver, BC, Canada aut Dutz Jan Department of Dermatology and Skin Science, The University of British Columbia, 835 West 10th Avenue, V5Z 4E8, Vancouver, BC, Canada aut Häfeli Urs Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, V6T 1Z3, Vancouver, BC, Canada aut Stoeber Boris Department of Electrical and Computer Engineering, The University of British Columbia, 5500 - 2332 Main Mall, V6T 1Z4, Vancouver, BC, Canada aut Biomedical Microdevices Springer US; http://www.springer-ny.com 17/3(2015-06-01), 1-10 1387-2176 17:3<1 2015 17 10544 https://doi.org/10.1007/s10544-015-9967-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10544-015-9967-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mansoor Iman Department of Electrical and Computer Engineering, The University of British Columbia, 5500 - 2332 Main Mall, V6T 1Z4, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Lai Jacqueline Department of Dermatology and Skin Science, The University of British Columbia, 835 West 10th Avenue, V5Z 4E8, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Ranamukhaarachchi Sahan Department of Electrical and Computer Engineering, The University of British Columbia, 5500 - 2332 Main Mall, V6T 1Z4, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Schmitt Veronika Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Lambert Dana Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Dutz Jan Department of Dermatology and Skin Science, The University of British Columbia, 835 West 10th Avenue, V5Z 4E8, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Häfeli Urs Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, V6T 1Z3, Vancouver, BC, Canada aut NATIONALLICENCE 700 1- Stoeber Boris Department of Electrical and Computer Engineering, The University of British Columbia, 5500 - 2332 Main Mall, V6T 1Z4, Vancouver, BC, Canada aut NATIONALLICENCE 773 0- Biomedical Microdevices Springer US; http://www.springer-ny.com 17/3(2015-06-01), 1-10 1387-2176 17:3<1 2015 17 10544