Brand, N; (2017) The Evaluation of Hand Sanitizer Formulations Based on the Characteristics of Stratum Corneum Lipids Processing Enzymes. Doctoral thesis , UCL (University College London).

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Abstract

Hand hygiene is a major and fundamental topic in patient management to avoid health care-associated infections. According to the WHO alcohol-based hand rubs are the preferred means in clinical antisepsis. However, the frequent use of alcohol-based hand rubs can cause adverse events, which negatively impact user compliance, demonstrating a risk for patients. Adverse events are based on protein denaturation and stratum corneum lipid extraction. The aim of this work was to develop in vivo assays for lipid-processing enzymes in the stratum corneum as biomarkers to be routinely used in the evaluation of hand sanitiser formulations. Tape stripping is a well-established method to obtain stratum corneum samples. Fluorogenic substrates were used to develop selective enzymatic assays for phospholipase A1, A2, lipase, β-glucocerebrosidase, and sphingomyelinase activity. Consecutive tapes were removed to understand the activity – depth profiles of the enzymes. In addition, the established non-invasive analytical methods of transepidermal water loss and spectrophotometric intracutaneous analysis were combined with the enzymatic measurements in clinical studies. The characteristic activity – depth profiles of enzymes changed under induced skin barrier alterations by ethanol exposure, indicating compensatory and inflammatory responses. In human subjects, the formulation containing of 0.4% glycerol in addition to 70% ethanol resulted in a reduced transepidermal water loss and reduced enzyme activity. This was based on its hydrating properties of the skin. Niacinamide at 0.3% added an additional benefit on barrier integrity, increasing cohesion between corneocytes and reduced lipase activity. Glycine has hydrating properties and was able to reduce transepidermal water loss added to the 70% ethanol formulation. Glycine increased the activity of β-glucocerebrosidase in healthy skin and hence also offers an interesting new approach in hand sanitisers by potentially altering the Cl- flux in keratinocytes increasing lamellar body secretion and delivering higher amounts of intercellular lipids. The successfully developed assays demonstrate a minimally invasive method to identify the state of the skin barrier integrity in human subjects. This approach allowed the identification of the benefits of glycerol, niacinamide, and glycine in hand sanitisers, regarding the skin barrier integrity. Further excipients and compositions can be routinely studied with these methods in the future to optimise hand sanitiser formulations and consequently improve user compliance. However, the assays are not limited to the evaluation of hand sanitiser but the biomarkers can also be applied to study other formulations or active pharmaceutical ingredients as well as in the understanding, characterization, and monitoring of disease states of the skin.

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