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Cellular metabolism and pore lifetime of human skin following microprojection array mediation
Curtin Univ, Australia; Univ Queensland, Australia.
Univ Queensland, Australia; Delft Univ Technol, Netherlands.
Univ Queensland, Australia.
Heriot Watt Univ, Scotland.
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2019 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 306, p. 59-68Article in journal (Refereed) Published
Abstract [en]

Skin-targeting microscale medical devices are becoming popular for therapeutic delivery and diagnosis. We used cryo-SEM, fluorescence lifetime imaging microscopy (FLIM), autofluorescence imaging microscopy and inflammatory response to study the puncturing and recovery of human skin ex vivo and in vivo after discretised puncturing by a microneedle array (Nanopatch (R)). Pores induced by the microprojections were found to close by similar to 25% in diameter within the first 30 min, and almost completely close by similar to 6 h. FLIM images of ex vivo viable epidermis showed a stable fluorescence lifetime for unpatched areas of similar to 1000 ps up to 24 h. Only the cells in the immediate puncture zones (in direct contact with projections) showed a reduction in the observed fluorescence lifetimes to between similar to 518-583 ps. The ratio of free-bound NAD(P)H (alpha 1/alpha 2) in unaffected areas of the viable epidermis was similar to 2.5-3.0, whereas the ratio at puncture holes was almost double at similar to 4.2-4.6. An exploratory pilot in vivo study also suggested similar closure rate with histamine administration to the forearms of human volunteers after Nanopatch (R) treatment, although a prolonged inflammation was observed with Tissue Viability Imaging. Overall, this work shows that the pores created by the microneedle-type medical device, Nanopatch (R), are transient, with the skin recovering rapidly within 1-2 days in the epidermis after application.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV , 2019. Vol. 306, p. 59-68
Keywords [en]
Skin, 3D confocal microscopy; Pore lifetime; Metabolic lifetime; Microneedles; Drug delivery; Histamine sensitisation, FLIM
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-159137DOI: 10.1016/j.jconrel.2019.05.024ISI: 000474822700005PubMedID: 31121279OAI: oai:DiVA.org:liu-159137DiVA, id: diva2:1339666
Note

Funding Agencies|Australian Research Council Centre of Excellence in Convergent Bio-Nano Science & Technology Grant [140100036CE]; Australian Research Council [DP1093281]; Australian National Health & Medical Research Council Fellowship [1107356]; Australian Government Research Training Program Scholarship; AIBN top up scheme; Curtin International Postgraduate Research Scholarship; LaVision MPM; Vaxxas; University of Queensland; Centre for Microscopy and Microanalysis; Australian Institute for Bioengineering and Nanotechnology; Princess Alexandra Hospital staff and skin donors

Available from: 2019-07-30 Created: 2019-07-30 Last updated: 2019-07-30

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Anderson, ChrisHenricson, Joakim
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Division of Cell BiologyFaculty of Medicine and Health SciencesDepartment of Dermatology and VenerologyDivision of Drug ResearchDepartment of Emergency Medicine
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