Publications

Filaggrin is one of the main skin proteins. Loss-of-function mutations of the filaggrin gene (FLG) lead to a much-increased risk of developing atopic dermatitis (AD). AD-patients with a FLG-mutations also tend to follow a more severe disease course and have a higher risk of co-morbidities. Over 50 different mutations have been identified, with the prevalence of specific mutations being geographically and ethnically determined. In the stratum corneum, filaggrin is enzymatically degraded into its constituting amino acids and amino acid derivatives, which form the bulk of the so-called natural moisturizing factor (NMF). Its hygroscopic properties keep the stratum corneum moisturized. The paper by Van Mierlo et al. shows that a simple and quick non-invasive determination Raman-analysis of the NMF-concentration in the stratum corneum on the palm of the hand, robustly predicts the presence of filaggrin mutations, independent of the specific FLG-mutation and not affected by actual disease status.

Dermal delivery of NIA was investigated in vivo in human subjects using confocal Raman spectroscopy (CRS) and tape stripping (TS).

• The vehicles investigated included propylene glycol (PG), Transcutol®P (TC), binary combinations of PG with oleic acid (OA) or linolenic acid (LA) and a ternary system comprising of TC, caprylic/capric triglyceride (CCT) and dimethyl isosorbide (DMI).
• For the CRS studies, higher area under curve (AUC) values for NIA were observed for the PG:LA binary system compared with PG, TC and TC:CCT:DMI (p < 0.05).
• A very good correlation was found between the in vitro cumulative permeation of NIA and the AUC values from Raman intensity depth profiles, with a Pearson correlation coefficient (R^2) of 0.84.
• In addition, an excellent correlation (R^2 = 0.97) was evident for the signal of the solvent PG and the active.
• CRS was also shown to discriminate between NIA in solution versus crystalline NIA.
• The findings confirm that CRS is emerging as a powerful approach for dermatopharmacokinetic studies of both actives and excipients in human

This article describes a unique noninvasive capability to determine the concentration (in mg/cm3) and total amount of topically applied materials in the skin (in μg/cm2 of skin surface). It is based on in vivo confocal Raman spectroscopy. A theoretical derivation is given of a general method to calculate a concentration ratio from a Raman spectrum of a material in a medium, which can be a solvent or other matrix, such as the skin. A practical implementation of the method is then presented along with a clarification of the assumptions used and applied to a quantitative analysis of the in vivo skin penetration of trans-retinol and propylene glycol (PG). A comparison was made between the concentrations profiles of retinol and PG found in the skin and the concentrations of retinol and PG that had been applied to the skin. Determination of the amount of these materials in the skin at different timepoints after topical application also enabled a straightforward calculation of the flux of materials into the skin (in μg cm−2 h).