Ts. Wiedmann et al., Distribution and diffusion of sodium taurocholate and egg phosphatidylcholine aggregates in rat intestinal mucin, PHARM RES, 18(11), 2001, pp. 1489-1496
Purpose. The permeability of rat intestinal mucin (RIM) to sodium taurachol
ate/egg phosphatidylcholine (TC/PC)-mixed micelles has been investigated.
Methods. The time dependence for the equilibration of TC/PC-mixed lipid mic
elles. with isolated RIM was determined. Thereafter the distribution of TC/
PC-inixed lipid micelles was assessed at low and high PC and intermicellar
concentrations (IMC) and with different RIM concentrations. The equilibrium
distribution of PC and TC was determined by analysis for phosphorus and by
high-performance liquid chromatography, respectively, as well as by nuclea
r magnetic resonance spectroscopy. In addition, the diffusion coefficients
of water, PC, and TC were measured by pulsed field gradient nuclear magneti
c resonance spectroscopy. Two model solutes, phenylmethyltrimethylsilane (P
TMS) and tetramethylsilyl-tetradeutero-proprionic acid (TSP), were added to
the high PC, low IMC samples, and the diffusion coefficients were determin
ed.
Results. The time to reach equilibrium was 2 days for a system with a high
intermicellar concentration of sodium taurocholate. At low PC concentration
s, RIM had slightly higher PC concentrations relative to the control. In co
ntrast, at high PC concentrations, RIM samples had lower PC concentrations.
The concentration of TC was largely independent of mucin concentration. Th
e water diffusivity was reduced proportionately to the concentration of RIM
, and analysis indicated that about 150 g of water moved as a kinetic unit
with each gram of mucin. The diffusion coefficients of PC were also reduced
with increasing RIM concentration. The magnetization decay of TC did not a
lways follow a monoexponential decay, reflecting the simultaneous diffusion
and exchange among sites imparting different relaxation behavior on the TC
. Magnetization decay curves were simulated and the diffusivity of TC in mu
cin was estimated. The diffusion coefficient of TSP was 10 times larger tha
n that of PTMS in the presence of micelles and mucin.
Conclusions. RIM is highly hydrated, and dilute solutions have a minor excl
usive effect on the high concentration of PC/TC micelles. At low concentrat
ions of PC, there appears to be preferential association of the PC with the
RIM. The permeability of mucin to solutes in the presence of bile salt mix
ed micelles critically depends on the degree of association of the solute w
ith the micelle.