Kendall D. Peck

Hindered Diffusion of Polar Molecules Through and Effective Pore Radii Estimates of Intact and Ethanol Treated Human Epidermal Membrane

The in vitro passive transport of urea, mannitol, sucrose and raffinose across intact and ethanol treated human epidermal membrane was investigated. The intent of this study was to characterize the barrier properties and permeation pathways of these membranes for polar permeants under passive conditions. Based upon the relative permeabilities of these four solutes and hindered diffusion theory, the experimental data was adequately modeled for both membrane systems according to permeation through a porous membrane. Effective pore radii estimates for intact human epidermal membrane fell between 15 Å to 25 Å while similar estimates fell compactly between 15 Å to 20 Å for ethanol treated human epidermal membrane. Similarities between the relative permeabilities of human epidermal membrane for the four permeants studied and the relative permeabilities of these same permeants through ethanol pretreated human epidermal membrane indicate that significant similarities exist between the permeation pathways for both membrane systems. The results of this study have important implications for transdermal drug delivery in general and more specifically for strategies of designing effective chemical permeation enhancement systems.

Improved stability of the human epidermal membrane during successive permeability experiments

Abstract In many cases it is instructive to use a single human epidermal membrane (HEM) sample to perform successive in vitro permeability experiments under varied experimental conditions. This study focused upon the feasibility of such successive permeability experiments in side-by-side, two-chamber diffusion cells. It was shown that for permeability experimental protocols which involved performing one permeability experiment per day and extensive washing between permeability experiments, the barrier properties of HEM samples were altered significantly within the first 72 h of the protocol. However, if the HEM is supported in the diffusion cell with a porous synthetic membrane, a single HEM sample remains essentially unaltered with respect to mannitol permeability and electrical resistance for up to 5 days. This suggests that protecting the HEM from physical stress is an essential element in performing successive permeability experiments.