Cellular metabolism and pore lifetime of human skin following microprojection array mediation

Isha N. Haridass, Jonathan C.J. Wei, Yousuf H. Mohammed, Michael L. Crichton, Christopher D. Anderson, Joakim Henricson, Washington Y. Sanchez, Stefano C. Meliga, Jeffrey E. Grice, Heather A.E. Benson, Mark A.F. Kendall, Michael S. Roberts

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)

Abstract

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®). Pores induced by the microprojections were found to close by ~25% in diameter within the first 30 min, and almost completely close by ~6 h. FLIM images of ex vivo viable epidermis showed a stable fluorescence lifetime for unpatched areas of ~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 ~518–583 ps. The ratio of free-bound NAD(P)H (α1/α2) in unaffected areas of the viable epidermis was ~2.5–3.0, whereas the ratio at puncture holes was almost double at ~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® 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®, are transient, with the skin recovering rapidly within 1–2 days in the epidermis after application.

Original languageEnglish
Pages (from-to)59-68
JournalJournal of Controlled Release
Volume306
DOIs
Publication statusPublished - 2019

Keywords

  • Drug delivery
  • Histamine sensitisation, FLIM
  • Metabolic lifetime
  • Microneedles
  • Pore lifetime
  • Skin, 3D confocal microscopy

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