The effect of the monosodium salt of a C 21 dicarboxylic acid hydrotrope on biosurfactant bilayers: Transdermal delivery considerations

Abstract

The lipids of the outermost layer of human skin are a unique non-viable biosurfactant system. Since these bilayer-structured lipids are primarily responsible for the skin's barrier function, a molecular understanding of how these lipids interact with a non-irritating monosodium salt of a C 12 dicarboxylic acid (NaDA) hydrotrope was investigated. Previous studies showed that this molecule dramatically disorders the lamellar liquid crystalline phase formed from a water/octanol/sodium octanoate mixture. If equivalent disordering of bilayer-structured epidermal lipids occurred, then NaDA would be an effective transdermal drug delivery enhancer. However, in-vitro transdermal measurements showed no increase in drug delivery after addition of 10 wt% NaDA to a well-characterized formulation. To further evaluate this mechanism, the bilayer disordering ability of NaDA was compared with sodium octanoate in four model systems, sodium octanoate/octanol/water, monocaprylin/water, lecithin/water, and lecithin/ethylene glycol. These lamellar liquid crystalline hosts have mean extrapolated amphiphilic interfacial surface areas of 25, 30, 53 , and 70 Å 2, respectively. Based on phase behavior studies, as the extrapolated interfacial area increased from 25 to 70Å 2, the effectiveness of NaDA to disorder the bilayer decreased an order of magnitude. Since the mean interfacial area for the bilayer-structured epidermal lipids was approximated to be in the range 34–38Å 2, the ineffectiveness of NaDA to enhance transdermal delivery was attributed to NaDA's inability to destabilize bilayers with extrapolated interfacial surface areas above approximately 32 Å 2 . The significance of NaDA selectively destabilizing bilayers of a specific dimension is discussed in this preliminary investigation, especially in terms of enhanced topical drug delivery.