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 molec ules, like many peptides and oligonucleotides, in the body. The parace llular pathway occupies a very small surface area and is sealed by the junctional complex. In many cases the paracellular pore size (r(p)) i s comparable with the radius of diffusing molecule (r(d)) and so calle d 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 use d to estimate pore sizes of the paracellular route and the porosity of the effective barrier of biomembranes. The model membranes were the c ornea and conjunctiva of a rabbit eye and the permeating paracellular probes were a mixture of 17 polyethylene glycols of different sizes. I t 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 appro ach yielded realistic values for the paracellular pore diameter and fo r the number of the pores in the cornea and conjunctiva. The theory wi ll evidently also be applicable to several other biomembranes, enablin g calculation of paracellular pore sizes and porosities; for example n asal, tracheal and intestinal epithelia should fulfill the criteria. ( C) 1997 Elsevier Science B.V.