Estimation of pore size and pore density of biomembranes from permeability measurements of polyethylene glycols using an effusion-like approach

Biomembranes restrict adsorption and distribution of hydrophilic molecules, like many peptides and oligonucleotides, in the body. The paracellular pathway occupies a very small surface area and is sealed by the junctional complex. In many cases the paracellular pore size (r(p)) is comparable with the radius of diffusing molecule (r(d)) and so called Renkin correction is used to model the transmembrane diffusion in a quantitative way. In this approach a crucial parameter r(d)/r(p) must not be greater than 0.3-0.4; a requirement that is not often fulfilled by experimental data. Consequently, an effusion-like approach was used to estimate pore sizes of the paracellular route and the porosity of the effective barrier of biomembranes. The model membranes were the cornea and conjunctiva of a rabbit eye and the permeating paracellular probes were a mixture of 17 polyethylene glycols of different sizes. It was concluded that the rate determining step for the permeability of the drug through the studied membranes is the probability of finding hydrophilic pores. Another criteria for the effusion-like process was that the effective barrier thickness is small. The effusion-like approach yielded realistic values for the paracellular pore diameter and for the number of the pores in the cornea and conjunctiva. The theory will evidently also be applicable to several other biomembranes, enabling calculation of paracellular pore sizes and porosities; for example nasal, tracheal and intestinal epithelia should fulfill the criteria. (C) 1997 Elsevier Science B.V.