Abstract
The in vitro models are receiving growing attention in studies on skin permeation, penetration, and irritancy, especially for the preclinical development of new transcutaneous drugs. However, synthetic membranes or cell cultures are unable to effectively mimic the permeability and absorption features of the cutaneous barrier. The use of explanted skin samples maintained in a fluid dynamic environment would make it possible for an in vitro experimentation closer to in vivo physiological conditions. To this aim, in the present study, we have modified a bioreactor designed for cell culture to host explanted skin samples. The preservation of the skin was evaluated by combining light, transmission, and scanning electron microscopy, for the histo/cytological characterization, with nuclear magnetic resonance spectroscopy, for the identification in the culture medium of metabolites indicative of the functional state of the explants. Our morphological and metabolomics results demonstrated that fluid dynamic conditions ameliorate significantly the structural and functional preservation of skin explants in comparison with conventional culture conditions. Our in vitro system is, therefore, reliable to test novel therapeutic agents intended for transdermal administration in skin samples from biopsies or surgical materials, providing predictive information suitable for focused in vivo research and reducing animal experimentation.
Highlights
The skin is a multilayered organ made of epidermis and dermis, each of which characterized by peculiar histological features and unique complementary functions
The skin barrier properties mostly rely on the stratum corneum, that is, the uppermost epithelial layer composed of differentiated anucleate cells, which are filled with keratins and embedded in a lipid domain
At LM, the skin samples did not show any sign of deterioration in both conventional and dynamic culture systems at all incubation times (Fig. 2): the epithelial layer was intact, the histological continuity between the epidermis and dermis and between the dermis and dermal adipose tissue was preserved, and the annexed structures such as glands and hair follicles were well-maintained
Summary
The skin is a multilayered organ made of epidermis and dermis, each of which characterized by peculiar histological features and unique complementary functions. The skin barrier properties mostly rely on the stratum corneum, that is, the uppermost epithelial layer composed of differentiated anucleate cells (the corneocytes), which are filled with keratins and embedded in a lipid domain. This highly hydrophobic layer is a so efficient barrier and that it hampers the uptake of active compounds for local or systemic therapeutic treatments. Due to the recently changed regulatory rules on animal testing, the in vitro models are receiving increased attention in the studies on skin permeation, penetration, and irritancy; for the preclinical experimentation of new drugs constructed for cutaneous administration, there is a growing interest for experimental systems able to effectively mimic the permeability and absorption features of the cutaneous barrier
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