The Influence of Various Freezing-thawing Methods of Skin on Drug Permeation and Skin Barrier Function.
AAPS J
; 26(4): 76, 2024 Jul 02.
Article
em En
| MEDLINE
| ID: mdl-38955873
ABSTRACT
The selection of skin is crucial for the in vitro permeation test (IVPT). The purpose of this study was to investigate the influence of different freezing-thawing processes on the barrier function of skin and the transdermal permeability of granisetron and lidocaine. Rat and hairless mouse skins were thawed at three different conditions after being frozen at -20â for 9 days thawed at 4â, room temperature (RT), and 32â. There were no significant differences in the steady-state fluxes of drugs between fresh and thawed samples, but compared with fresh skin there were significant differences in lag time for the permeation of granisetron in rat skins thawed at RT and 32â. Histological research and scanning electron microscopy images showed no obvious structural damage on frozen/thawed skin, while immunohistochemical staining and enzyme-linked immunosorbent assay for the tight junction (TJ) protein Cldn-1 showed significantly impaired epidermal barrier. It was concluded that the freezing-thawing process increases the diffusion rate of hydrophilic drugs partly due to the functional degradation of TJs. It's recommended that hairless, inbred strains and identical animal donors should be used, and the selected thawing method of skin should be validated prior to IVPT, especially for hydrophilic drugs.
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Base de dados:
MEDLINE
Assunto principal:
Permeabilidade
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Pele
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Absorção Cutânea
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Congelamento
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Camundongos Pelados
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article