Km. Hamalainen et al., ESTIMATION OF PORE-SIZE AND PORE DENSITY OF BIOMEMBRANES FROM PERMEABILITY MEASUREMENTS OF POLYETHYLENE GLYCOLS USING AN EFFUSION-LIKE APPROACH, Journal of controlled release, 49(2-3), 1997, pp. 97-104
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.