Li YZ, Quan YS, Zang L, Jin MN, Kamiyama F, Katsumi H, Tsutsumi S, Yamamoto A.
Institute for Frontier Medical Science, Kyoto University, Shogoin, Sakyo-ku, Japan.
OBJECTIVES: The aim was to assess the effect of trypsin on the transdermal delivery of macromolecules by applying its specific biochemical properties to the stratum corneum of the skin. METHODS: Fluorescein isothiocyanate (FITC)-labelled dextrans (FDs), with molecular weights of 4 to 250 kDa, and FITC-insulin were used as model macromolecules and a model polypeptide, and the in-vitro transdermal permeation experiments, with or without trypsin (0.1-2.5%), were carried out using rat skin and cultured human epidermis. The mechanism for the enhancement of trypsin was also studied using fluorescence and conventional light microscopy. KEY FINDINGS: Trypsin significantly increased the transdermal permeability of all FDs through the rat skin (2.0- to 10.0-fold). It also markedly enhanced the permeation of FD4 through three-dimensional cultured human epidermis (3.1-fold), which was used to evaluate the transport pathways other than the transfollicular route. Furthermore, the permeation flux of FITC-insulin was increased by 10.0-fold with trypsin pretreatment (from 0.02 +/- 0.00 to 0.20 +/- 0.07 microg/cm(2) per h). Mechanistic studies indicated that trypsin affects both the intercellular pathway and the hair follicular route, and may alter stratum corneum protein structures, thereby affecting skin barrier properties. CONCLUSIONS: This study suggests that trypsin could be effective as a biochemical enhancer for the transdermal delivery of macromolecules including peptide and protein drugs.
PMID: 19703343
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