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Distribution and Diffusion of Sodium Taurocholate and Egg Phosphatidylcholine Aggregates in Rat Intestinal Mucin

Research paper by Timothy Scott Wiedmann, Heather Herrington, Cinthia Deye, Deborah Kallick

Indexed on: 01 Nov '01Published on: 01 Nov '01Published in: Pharmaceutical Research



Abstract

Purpose. The permeability of rat intestinal mucin (RIM) to sodium taurocholate/egg phosphatidylcholine (TC/PC)-mixed micelles has been investigated.Methods. The time dependence for the equilibration of TC/PC-mixed lipid micelles with isolated RIM was determined. Thereafter the distribution of TC/PC-mixed 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 nuclear magnetic resonance spectroscopy. In addition, the diffusion coefficients of water, PC, and TC were measured by pulsed field gradient nuclear magnetic resonance spectroscopy. Two model solutes, phenylmethyltrimethylsilane (PTMS) and tetramethylsilyl-tetradeutero-proprionic acid (TSP), were added to the high PC, low IMC samples, and the diffusion coefficients were determined.Results. The time to reach equilibrium was 2 days for a system with a high intermicellar concentration of sodium taurocholate. At low PC concentrations, RIM had slightly higher PC concentrations relative to the control. In contrast, at high PC concentrations, RIM samples had lower PC concentrations. The concentration of TC was largely independent of mucin concentration. The 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 always 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 mucin was estimated. The diffusion coefficient of TSP was 10 times larger than that of PTMS in the presence of micelles and mucin.Conclusions. RIM is highly hydrated, and dilute solutions have a minor exclusive effect on the high concentration of PC/TC micelles. At low concentrations 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 mixed micelles critically depends on the degree of association of the solute with the micelle.