]. Cosmet. Sci., 58, 651-662 (November/December 2007) Water-handling properties of vernix caseosa and a synthetic analogue ANYARPORN TANSIRIKONGKOL, MARTY 0. VISSCHER, and R. RANDALL WICKETT, College of Pharmacy (A.T., R.R. W.) and Skin Sciences Institute, Children's Hospital Research Foundation (M.O.V.), University of Cincinnati, Cincinnati, OH 45267. Accepted for publication May 14, 2007. Synopsis A naturally occurring barrier cream, vernix caseosa, is the viscous material synthesized by the sebaceous glands in the late gestational human fetus. Vernix functions as a moisturizer by increasing the skin hydration and water-holding capacity of treatcd skin. Vernix films are semi-permeable, i.e., in the range that facilitates barrier repair. Antioxidant, disinfectant, and skin cleansing functions are also present. Premature infants have a markedly immature epidermal barrier and the excessive water loss can lead to fluid and electrolyte imbalances, along with high evaporative heat loss. Application of petrolatum-based, low-water creams on these infants has decreased TEWL and improved the skin condition. However, in infants of 500-750 g, this treatment was associated with an increased incidence of late-onset nosocomial infection, and questions regarding efficacy and safety have been raised. The water-handling properties, semi-permeability and multi-functionality, suggest that application of vernix may promote the development and restoration of premature or other compromised skin. The present study focuses on the development of barrier creams to simulate the water-handling properties of native vernix. Barrier creams were prepared as high-water-phase emulsions containing various lipid mixtures. Several stable creams with high water content exhibited slow water release and water vapor transport rates in the range to facilitate barrier repair. The results showed the importance of emulsion type in preventing water release. Preparations with vernix-like lipids demonstrated water release profiles closer to the native vernix benchmark than those with conventional lipids. The work resulted in a synthetic vernix barrier cream prototype for evaluation on skin and to which additional functionality, e.g., anti-infective and antioxidant activity, could be added. INTRODUCTION Vernix caseosa is a biological material coating the fetal skin surface during the last trimester of gestation. The production of vernix coincides with the presence of a ter­ minally differentiated epidermis as seen by the formation of the fetal stratum corneum (SC) (1,2). The amount and distribution of native vernix vary among infants depending upon gestational age, delivery mode, gender, race, and meconium exposure (3). Vernix Address all correspondence to Marty 0. Visscher. 651

652 JOURNAL OF COSMETIC SCIENCE usually remains in the skin creases and hair of term newborn infants. However, it is absent in the very-low-birthweight premature infants. Low-birthweight preterm infants have a markedly immature epidermal barrier (4), demonstrating a thin and poorly formed stratum corneum. One of the most important problems due to this ineffective barrier function is the excessive water loss during the first few days following birth (5-7). High transepidermal water loss (TEWL) may lead to life-threatening problems, such as fluid and electrolyte imbalances and high evapo­ rative heat loss. Attempts have been made to reduce high TEWL in premature infants by the use of occlusive barriers such as hydrophobic polymer films or topical agents. A topical emollient containing petrolatum, e.g., Aquaphor®, is often applied in the nurs­ ery to retain moisture and to provide protection for immature skin. Such treatment has been reported to decrease TEWL and improve skin condition (8-10). However, a more recent study demonstrated an increased incidence of late-onset nosocomial infection secondary to coagulase-negative staphylococci in infants of 500-750 grams (11). There­ fore, the efficacy and safety of topical emollient use in this population has been ques­ tioned. A naturally occurring barrier cream, vernix caseosa, is a viscous whitish material syn­ thesized by the late gestational human fetus. It is a structurally simpler system than SC, comprised of a nonlamellar lipid matrix containing fetal corneocytes without cell-to-cell desmosome connections (12,13). Vernix has been described as a mobile-phase SC. Com­ positionally, vernix is mainly composed of water (80%), protein (9.1 %) and lipid (10.3%) (14). The lipid phase of vernix has been identified as a composition of sebaceous lipids and stratum corneum lipids (14,15). It provides a large quantity of slowly releas­ able water. Vernix has been shown to increase skin hydration and the water-holding capacity of treated skin, suggesting a moisturizing property (15,16). Additionally, ver­ nix films are semi-permeable to water vapor and provide water vapor transport in the range that facilitates barrier repair ( 17). Other properties of vernix include antioxidant (18), disinfectant (19-21) and natural skin cleanser (22) functions. Vernix may represent a system that would facilitate adaptation of the epidermal barrier at birth. Because of the multiple functions and unique water-handling properties (23), application of vernix may promote the development and restoration of premature or other compromised skin. However, natural vernix obtained from newborn infants is very limited in quantity. It is not feasible to topically apply vernix obtained from one infant to another because of the risk of infection. Therefore, there was a need for a new barrier cream based on native vernix as a prototype. The present study focuses on the development of barrier creams to simulate the water­ handling properties of native vernix (23 ). Barrier creams were prepared as high-water­ phase emulsions. Composition of the lipids and emulsifiers was selected based upon the results of emulsion stability testing and water-handling properties. The water release rate and water vapor transport rate were assessed using methods modified by our labo­ ratory (23). MATERIAL AND METHODS MATERIALS The raw materials and suppliers are as follows: light mineral oil and white petrolatum (Penreco, Dickinson, TX), lanolin (Amerchol, Piscataway, NJ), stearyl alcohol (Spectrum