Skin permeability barrier is composed partly by cornified lipid lamellae and partly by tight junctions located in the epidermis, and disturbances in this barrier may result various diseases.

We investigated the effect of organic osmolyte candidates, betaine, L-proline, L-serine and myo-inositol, as combination (in amounts as in GENENCARE® OSMS PRO) and as single compounds, and their contribution to skin barrier function by two exemplary methods: analyzing the diffusion of topically applied caffeine through reconstructed human epidermis (RHE) and by measuring transepithelial electric resistance (TEER) of differentiated normal human epidermal keratinocytes (NHEKs).

RHE were treated with the osmolytes systemically, and the diffusion of radioactive [14]C¬caffeine through the RHE was followed. NHEK cells were cultured on inserts and after three days of differentiation in high calcium concentration, the test substances were applied apically to the cells, and the effect on tight junction integrity was measured using chopstick electrodes.

The systemic osmolyte combinations of betaine, L-proline, L-serine and myo-inositol (3 and 10 mg/ml), induced a decrease of caffeine diffusion through the RHE, during the first two hours with a significant effect at 30 min and 1 h compared to medium control, indicating stronger epidermal structure and barrier function in the osmolyte treated RHE. Betaine alone (3 mg/ml) induced a decrease of caffeine diffusion also after 30 min and 1 h, while L-proline alone (3 and 10 mg/ml) did not decrease caffeine diffusion. Application of topical osmolyte combination (10 mg/ml) resulted increase in %change in TEER values of 28% (at 2 h), 28% (at 3 h) and 43% (at 5 h) compared to medium control without osmolytes having %change in TEER -5 %, -6 % and 14 %, respectively. 0.15 M NaCl, which modelled the hyperosmotic stress, resulted significant decrease in %change in TEER in all time points.

The results indicate that organic osmolytes may have beneficial effects on epidermal permeability barrier and tight junction integrity, that might be especially advantageous during a stress compromising the function of the tight junctions and permeability barrier.

Effect of organic osmolytes improving skin’s barrier function