Utility of Three-Dimensional Skin From Human-Induced Pluripotent Stem Cells as a Tool to Evaluate Transdermal Drug Permeation.
Administration, Cutaneous
Animals
Cells, Cultured
Dextrans
/ metabolism
Drug Delivery Systems
/ methods
Epidermis
/ metabolism
Fibroblasts
/ metabolism
Fluorescein-5-isothiocyanate
/ analogs & derivatives
Humans
Induced Pluripotent Stem Cells
/ metabolism
Keratinocytes
/ metabolism
Permeability
/ drug effects
Pharmaceutical Preparations
/ metabolism
Skin
/ metabolism
Skin Absorption
/ drug effects
absorption
drug delivery system(s)
skin
transdermal
Journal
Journal of pharmaceutical sciences
ISSN: 1520-6017
Titre abrégé: J Pharm Sci
Pays: United States
ID NLM: 2985195R
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
30
05
2019
revised:
08
07
2019
accepted:
17
07
2019
pubmed:
28
7
2019
medline:
9
9
2020
entrez:
28
7
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31351104
pii: S0022-3549(19)30441-1
doi: 10.1016/j.xphs.2019.07.006
pii:
doi:
Substances chimiques
Dextrans
0
Pharmaceutical Preparations
0
fluorescein isothiocyanate dextran
0
Fluorescein-5-isothiocyanate
I223NX31W9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3524-3527Informations de copyright
Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.