Porous permeation pathway

With an experimental protocol in place that facilitated studies aimed at characterizing the porous permeation pathway, a systematic study of polar compound permeation through HEM was undertaken (Peck et al., 1994). As has already been described, there is a void in the literature with respect to the passive permeation of polar solutes through skin. The initial purpose of the studies outlined in this section was to add to the polar solute permeation database. An effort was again made to determine the degree to which the barrier characteristics of skin with respect to polar compounds approach, or deviate from, those of an ideal porous membrane. 

Based upon the justification for the existence of a porous permeation pathway provided by the data outlined thus far in this chapter, a reasonable theoretical starting point for these studies is the simple equation that relates the permeability coefficient, P, of the solute through a porous membrane to its diffusion coefficient in the membrane, D. ... 

Based upon Eq. 4 a systematic study was performed with four polar permeants (urea, mannitol, sucrose, and raffinose) in an effort to characterize further the porous permeation pathway through HEM (Peck et al., 1994). Dual-labeled liquid scintillation counting and an experimental protocol that incorporated successive permeability experiments, as outlined in the previous sections, allowed the permeability coefficients for each permeant to be determined for each HEM sample studied. Again, Eq. 4 predicts that, for a porous membrane, the permeability coefficient ratio should be equal to the ratio of the diffusion coefficients for the solutes in the membrane. As a first approximation, if the relative radii of the solutes and the membrane pore radii Rp are such that hindrance considerations are negligible (Deen, 1987), then the ratio PJPy should approach the ratio of the free diffusion coefficients D of the solutes in bulk solution. 

The systematic study of polar permeant permeation served to confirm the existence of a porous permeation pathway through the HEM. It also led to the characterization of important properties of this pathway. The results of this study demonstrated that the diffusion of polar permeants through skin is limited by the low effective porosity of the HEM and by hindrance effects due to restrictive pore dimensions. Effectively enhancing the transport of polar drugs in the MW range of many therapeutic peptides may require increasing the effective Rp of the HEM as well as the effective porosity/tortuosity ratio. Perhaps novel combinations of chemical permeation enhancers and physical means such as an applied electrical field or ultrasound may be necessary to achieve this objective. 

For a number of years the existence of a porous or polar pathway through the stratum comeum, in parallel with the lipoidal pathway, has been hypothesized. Although there has been some criticism of this concept, it is our belief that the root of the lack of a common consensus among scientists in the field can be attributed largely to the limited number of systematic studies in the literature that directly address the issue of the diffusion of polar and ionic permeants across skin. Based upon recent studies that have focused upon this aspect of transdermal diffusion, the existence of a porous permeation pathway through HEM is clear (Hatanaka et al., 1993, 1994 Peck et al., 1993, 1994, 1995). At this point, we have made no attempt to correlate the findings from our studies with specific structural properties of the HEM. In some cases, authors have implicated shunt routes such as hair follicles and sweat ducts to account for permeation data not consistent with the concept of lipoidal membrane permeation (Cornwell and Barry, 1993 Scheuplein and Blank, 1971). Under ionto-phoretic conditions, such shunt routes have been shown to contribute to current conduction (Cullander and Guy, 1991 Scott et al., 1993). When efforts have been made to estimate the effective Rp of skin samples under iontophoretic conditions (Ruddy and Hadzija, 1992), osmotic conditions (Hatanaka et al.,... 

Polar Cell Systems for Membrane Transport Studies Direct current electrical measurement in epithelia steady-state and transient analysis, 171, 607 impedance analysis in tight epithelia, 171, 628 electrical impedance analysis of leaky epithelia theory, techniques, and leak artifact problems, 171, 642 patch-clamp experiments in epithelia activation by hormones or neurotransmitters, 171, 663 ionic permeation mechanisms in epithelia biionic potentials, dilution potentials, conductances, and streaming potentials, 171, 678 use of ionophores in epithelia characterizing membrane properties, 171, 715 cultures as epithelial models porous-bottom culture dishes for studying transport and differentiation, 171, 736 volume regulation in epithelia experimental approaches, 171, 744 scanning electrode localization of transport pathways in epithelial tissues, 171, 792. 

In several cases, when the electrocatalytic pathway involves adduct formation between immobilized units of the catalyst and the mobile substrate permeating the porous solid, the mechanism can be described in terms of a charge transfer process preceded by a relatively slow chemical reaction. Here, the chronoamperometric current can be approached by (Koutecky and Brdicka, 1947 Bard and Faulkner, 2001) ... 

The filter medium is the core of the whole filtration process. A premium filter with a desired selectivity should have a defined pore size and a narrow pore size distribution. In addition, filters with high porosity, smooth surface, and liquid affinity should be beneficial toward a higher permeation rate and lower fouling, as the feed liquid is being passed from the filter surface into the porous pathway inside the filter. 

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