LATERAL DIFFUSION OF SMALL COMPOUNDS IN HUMAN STRATUM-CORNEUM AND MODEL LIPID BILAYER SYSTEMS

An image-based technique of fluorescence recovery after photobleaching (video-FRAP) was used to measure the lateral diffusion coefficients o f a series of nine fluorescent probes in two model lipid bilayer syste ms, dimyristoylphosphatidylcholine (DMPC) and DMPC/cholesterol (40 mol %), as well as in human stratum corneum-extracted lipids. The probes w ere all lipophilic, varied in molecular weight from 223 to 854 Da, and were chosen to characterize the lateral diffusion of small compounds in these bilayer systems. A clear molecular weight dependence of the l ateral diffusion coefficients in DMPC bilayers was observed. Values ra nged from 6.72 x 10(-8) to 16.2 x 10(-8) cm(2)/s, with the smaller pro bes diffusing faster than the larger ones. Measurements in DMPC/choles terol bilayers, which represent the most thorough characterization of small-solute diffusion in this system, exhibited a similar molecular w eight dependence, although the diffusion coefficients were lower, rang ing from 1.62 x 10(-8) to 5.60 x 10(-8) cm(2)/s. Lateral diffusion mea surements in stratum corneum-extracted lipids, which represent a novel examination of diffusion in this unique lipid system, also exhibited a molecular weight dependence, with values ranging from 0.306 x 10(-8) to 2.34 x 10(-8) cm(2)/s. Literature data showed that these strong mo lecular weight dependencies extend to even smaller compounds than thos e examined in this study. A two-parameter empirical expression is pres ented that describes the lateral diffusion coefficient in terms of the solute's molecular weight and captures the size dependence over the r ange examined. This study illustrates the degree to which small-molecu le lateral diffusion in stratum corneum-extracted lipids can be repres ented by diffusion in DMPC and DMPC/cholesterol bilayer systems, and m ay lead to a better understanding of small-solute transport across hum an stratum corneum.