DISTRIBUTION AND TRANSPORT OF LIPIDS IN MUCIN GELS

Mucus occurs throughout the body at epithelial surfaces in the trachea, gall bladder, cervix, eye, bladder, and in saliva as well as along the gastrointestinal tract. Each surface is exposed to lipids which modulate the viscoelasticity of mucin, but the specific physical chemical interactions between the lipid and mucin remain obscure. A clarification of these interactions would greatly enhance the understanding of these important lipid/mucus systems. In this proposal, the mechanism by which low water soluble compounds are transported through the mucous layer of the intestinal tract will be quantitatively examined. The hypothesis to be tested is that the association of lipids with mucin quantitatively affects the intestinal absorption of lipids and poorly water soluble drugs. The hypothesis will be tested by preparing a series of bile salt/phospholipid (BS/PC) samples of equal chemical potential but with variable intestinal mucin concentration be a dialysis technique, and then determining the concentrations of each component and the solution density. The effective diffusivity of water, phospholipids, and bile salt will be measured by FT-PFGSE NMR spectroscopy. From these observables, the size, shape, hydration and charge of the lipid aggregates in the presence and absence of mucin will be obtained. In addition, the hydration excluded volume and electrostatic exclusion effect (Donnan effect) of mucin an the affinity and capacity of mucin for the lipid will be determined. This approach will define the limiting physical chemical principles that determine the equilibrium distribution and dynamic properties of lipids in mucous gels. The diffusion coefficients of a series of p-n-alkyl benzoic acid and aniline derivatives will be measured in the bile salt monomer, bile salt/phospholipid, and the BS/PC/mucin solutions. By examining the diffusion coefficients with increasing PC concentration at constant mucin concentration, the existence and phase boundaries of a tricontinuous phase can be determined. Thus, the role of lipid-mucin interactions in the absorption of low water soluble nutrients and drugs will be obtained. Moreover, elucidation of the limiting physical chemistry of lipids and mucin will form the basis for the structure/function of mucous membranes throughout the body.