Utility of Three-Dimensional Skin From Human-Induced Pluripotent Stem Cells as a Tool to Evaluate Transdermal Drug Permeation

J Pharm Sci. 2019 Nov;108(11):3524-3527. doi: 10.1016/j.xphs.2019.07.006. Epub 2019 Jul 24.

Abstract

Transdermal drug delivery is an attractive route for administration of drugs, and it offers several advantages such as painless administration. To accurately predict the rate of human skin permeation for new transdermal drug formulations, we developed a novel assessment system using induced pluripotent stem cells (iPSCs). Skin was generated from iPSC-derived keratinocytes and fibroblasts. In the histological and immunohistochemical examination, cellular markers (keratin 14 and keratin 10) for the epidermal basal and suprabasal layers were clearly detected within the multilayer structures produced in the human iPSC-based three-dimensional skin model. The results from our permeation study indicate that an initial lag time exists during permeation of 5(6)-carboxyfluorescein and fluorescein isothiocyanate dextran 4000. Furthermore, the permeation for these model drugs in human iPSC-based skin was inversely proportional to the molecular weight of the drugs. These results of the present iPSC-based skin are useful basic information as a first step for developing a new assessment system to predict the efficacy of drug permeation in human skin by using iPSC-based skin.

Keywords: absorption; drug delivery system(s); skin; transdermal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Cells, Cultured
  • Dextrans / metabolism
  • Drug Delivery Systems / methods
  • Epidermis / metabolism
  • Fibroblasts / metabolism
  • Fluorescein-5-isothiocyanate / analogs & derivatives
  • Fluorescein-5-isothiocyanate / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Keratinocytes / metabolism
  • Permeability / drug effects*
  • Pharmaceutical Preparations / metabolism*
  • Skin / metabolism*
  • Skin Absorption / drug effects

Substances

  • Dextrans
  • Pharmaceutical Preparations
  • fluorescein isothiocyanate dextran
  • Fluorescein-5-isothiocyanate