Pilot Evaluation of a Novel Topical Formulation Containing High Level, Cholesterol-Dominant, Physiological Lipids for Specific Targeting of Skin Barrier Deficits in Aging Skin

Background: Topical products with epidermal lipids in a ceramide-dominant ratio were originally developed to address atopic dermatitis. They have been used by extension to address the barrier deficits of aging skin, and after laser resurfacing and other barrier-disrupting procedures. The purpose of this study was to evaluate efficacy, tolerability, and safety of a novel formulation containing high levels of physiological barrier lipids, in a unique cholesterol-dominant ratio hypothesized to directly address the specific epidermal lipid imbalances of aging skin. Methods: An 8-week, single-center study was conducted on females aged 55 to 75 with mild to moderate fine lines and wrinkles, and other stigmata of facial photodamage. Evaluations were performed at baseline, immediately after first use of the cholesterol-dominant test formulation, and at weeks 4 and 8. Efficacy evaluations comprised blinded expert grading of 9 skin attributes, bioinstrumental measurements of trans-epidermal water loss (TEWL) and stratum corneum hydration, standardized digital imaging, and self-assessment questionnaires. Tolerability was scored objectively and subjectively, and by grading of skin dryness. Adhesive tape extracts were analyzed biochemically for epidermal lipids, and by double-staining to detect mature vs. immature corneocytes. In a separate study, the effects of pre- or post-treatment with the test formulation on barrier recovery following traumatic tape stripping of forearm skin were assessed via measurements of TEWL and stratum corneum hydration. Results. Statistically significant improvements occurred in all facial skin attributes (weeks 4 and 8), TEWL (week 8), and stratum corneum hydration (weeks 4 and 8). There were significant increases in total ceramides and cholesterol, including ceramide isoforms not present in the test formulation itself; and a statistically significant increase in the ratio of mature to immature corneocytes at week 8. Forearm skin treated with the test formulation after traumatic tape stripping recovered barrier function significantly faster than untreated skin. Pre-treatment for 1 week prior to traumatic tape stripping had a significant protective effect. Tolerability and safety of the test formulation were excellent. Conclusions. This cholesterol-dominant lipid formulation offers a new paradigm of primary skin barrier repair specifically targeted toward aging skin. Correction of age-related epidermal lipid deficits directly addresses the underlying cause and the profound sequelae of barrier dysfunction in aging skin. This may also be of utility to optimize skin tolerance, response and recovery from aesthetic procedures and other topical treatments, and for dermatoses associated with barrier dysfunction, such as rosacea. The formulation achieved sustained improvements in barrier function throughout the course of the 8-week study, had a protective effect when applied prior to barrier insult, and mediated more rapid recovery when applied after barrier insult. Significant increases in total epidermal ceramides, cholesterol and triglycerides, and in mature versus immature corneocytes, indicated both structural and functional normalization of the skin barrier, and possibly a broader-based stimulation of ceramide synthesis. The formulation had excellent tolerability and safety profiles, even in subjects with sensitive skin.