Introduction
An increasingly prevalent disease in our aging society is diabetes, a condition that also exerts dramatic effects on the skin including dryness, itchiness, delayed wound healing and reduced barrier function. Current treatments with urea and greasy occlusive formulations are limited, and often only treat the symptoms without addressing or preventing the underlying cause of damaged diabetic skin. One major cause of a disrupted skin barrier function is a reduced or defective calcium gradient in the epidermis. The collapsed calcium gradient is also evident in very aged non-diabetic skin, resulting in disrupted skin homeostasis, reduced barrier function and epidermis thinning. Consequently, a potential therapeutic approach could be to replenish the calcium stores of diabetic and aged skin with topically applied calcium. In this study we investigated the potential of a novel Ca²⁺ double cone carrier system in improving epidermal barrier function and protection in vitro and in a clinical trial in vivo.
Methods
The Ca²⁺ double cone vector system used in this study was generated according to our novel patent-pending protocol. The mixing of negatively charged phospholipids with Ca²⁺ ions by high pressure homogenization results in supra-molecular cochleate with a double cone structure. This technology makes the Ca²⁺ ions bioavailable to the skin. The effect of this calcium delivery system on the differentiation of reconstructed human epidermis (RHE) was investigated at a low basal calcium condition (0.3 mM) to represent a diabetic or aged skin. The RHE was treated topically either with the calcium delivery system or with CaCl₂. The stratification of the epidermis and the expression of loricrin were then investigated. Further, the protective and regenerative effect of the topical application of our novel Ca²⁺ vector system was investigated in vivo. In a randomized placebo-controlled clinical study the skin barrier of 20 healthy volunteers was challenged with 2% sodium lauryl sulphate (SLS) for 24 hours under occlusion, following and/or prior to treatment with a gel containing 2% of our calcium vector system.
Results
The RHE culture in reduced basal calcium conditions (0.3mM), mimicking a diabetic skin condition, strongly impeded the formation of a dense stratified epidermis. The apical treatment with 1.1 mM CaCl₂ was not able to restore a functional differentiation as observed in the control of the RHE with a basal 0.3 mM CaCl₂ concentration. Instead, this negative effect was even further exacerbated with the apical treatment of 1.1 mM CaCl₂. On the other hand, treatment with 0.1 % of the Ca²⁺ double cone vector system rescued the differentiation process, prevented the formation of vacuoles, and increased the expression of the epidermal differentiation marker loricrin, resulting in a normal stratified epidermis. These positive effects or this Ca²⁺ vector system could be confirmed in a clinical study. The application of the Ca²⁺ double cone vector system prior to and following SLS stress prevented increases in skin irritation (as measured by skin microcirculation and skin redness) and transepidermal water loss (TEWL) compared to placebo controls. Importantly, in comparison to placebo controls, treatment with the Ca²⁺ vector system also accelerated the recovery time following SLS stress.
Discussion and Conclusion
Our data demonstrate the successful application of our novel patent-pending Ca²⁺ vector system on stressed skin. The delivery of bioavailable Ca²⁺ ions to the skin is a new approach to treat damaged barrier functions of the epidermis present in diabetic, aged or atopic skin. Such potential treatment avenues provide exciting new foundations for cosmetic treatments of skin impairments and should be addressed in future investigations. We believe that the treatment of diabetic skin will be a new important market for the cosmetic industry and that the provision of novel active ingredients such as this Ca²⁺ double cone vector system will contribute to a better healthy aging.