ROLES OF VEHICLES FOR SKIN TREATMENT 199 not down-regulate the physiological lipid synthesis (56,100). These studies support the hypothesis that the epidermis can internalize and process physiologic lipids. In contrast, non-physiologic lipids like petrolatum appear to simply form a bulk hy drophobic phase in the stratum corneum intercellular spaces to restore the permeability barrier under similar conditions (56,83). The same studies showed further enhancement of barrier recovery if the proportion of one of the fatty acids (linoleic acid, palmitic acid, or stearic acid) or the other key species was augmented threefold in a four-component system, i.e., consisting of fatty acid, ceramide, cholesterol, and essential fatty acids in a 3:1:1:1 ratio (57). Interestingly, the structural requirements of this lipid mixture are not restricted to essential fatty acids, a finding that was confirmed in a similarly disrupted human barrier (5 7). Interestingly, acylceramides applied as a single agent delayed barrier recovery. However, acylceramides in a mixture with cholesterol (optimum ratio of 1.5:1 or 1:2, respectively) also revealed accelerated barrier recovery after acute barrier disrup tion (57). Moreover, in another study, stratum corneum hydration (measured by con ductance) was increased four hours after topical application of a cholesterol-, acylce ramide-, petrolatum-, and glycerol-containing vehicle (propylene glycol/ethanol) (101). These findings were confirmed, as accelerated barrier repair was noted using a similar Stratum corneum -- Stratum granulosum _ ........ Figure 3. Putative route of incorporation and processing of exogenous physiologic lipids within cells of the outermost granular layer. Exogenous lipids may be delivered by an endocytic pathway to the trans-Golgi complex. These lipids become available for the lamellar body formation. [From Mao-Qiang, Brown, et al., 1995 (ref. 56), with permission.}
200 JOURNAL OF COSMETIC SCIENCE formulation after tape stripping, solvent treatment, and some types of detergent treat ment (102). Specifically, topical application of the physiologic lipids cholesterol, cer amide, palmi tate, and linoleate in the ration of 4. 3: 2. 3: 1: 1. 08 showed enhanced barrier recovery. However, it must be noted that in barrier repair-vs-hydration studies, corre lations between the moisturizing properties and barrier repair mechanism of applied lipid mixtures are not always evident. Actually, the best hydrating lipid composition is often different from the optimal barrier repair formulation and vice versa (101). FROM OLD TO NEW CONCEPTS Classical vehicles in dermatology are amphiphilic systems (60). An example is given from the German pharmacopoia: Base cream DAC Glycerol monostearate 60 Cetyl alcohol Mid-chain triglycerides White petrolatum Macrogol-1000-gl ycerol monostearate Propylene glycol Purified water 4.0 6.0 7.5 25.5 7.0 10.0 40.0 The problem with these formulations is the high content of emulsifiers that might have a negative effect on long-term application or counteract the positive features of the vehicles. A new approach is the use of hydrogenated polydecenes. They are special oligomers of decene, with branched isoparaffinic structures completely saturated after full hydroge nation. It has been shown that they are soluble in most nonpolar solvents and can be blended with common lipids. They spread easily, do not interfere negatively with the skin barrier, and are not occlusive (77). An example of a cream is given as follows: Allantoin Trimethylglycine Panthenol Carbomer Hydrogenated polydecene (NB 2004 FG)4 Limnanthes alba + butyrospermum parkii PPG-15 stearyl ether (a) Steareth-2 (b) Steareth-21 (c) Preservatives Tocopheryl acetate Sodium hydroxide Actives Purified water 4 Fortum Oil and Gas Oy, Base Oils, P.O. Box 100, 00048 Fortum, Finland. 0.10 1.00 0.20 0.50 6.50 2.50 1.00 2.00 1.00 q.s. 0.50 0.2 q.s. ad 100.00
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