Hydrogels and Cubic Liquid Crystals for Non-Invasive Sampling of Low-Molecular-Weight Biomarkers-An Explorative In Vivo Study

Pharmaceutics. 2022 Jan 28;14(2):313. doi: 10.3390/pharmaceutics14020313.


The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels.

Keywords: electrical impedance spectroscopy; kynurenine; low-molecular-weight biomarker; natural moisturizing factor; phenylalanine; skin barrier integrity; stratum corneum; transepidermal water loss; tryptophan; tryptophan-to-kynurenine ratio; tyrosine.