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  • Title: Interaction of bile salt and phospholipids with bovine submaxillary mucin.
    Author: Wiedmann TS, Deye C, Kallick D.
    Journal: Pharm Res; 2001 Jan; 18(1):45-53. PubMed ID: 11336352.
    Abstract:
    PURPOSE: The purpose of this study was to determine the distribution and diffusion of sodium taurocholate-phospholipid micelles with mucin in order to provide the foundation for understanding the transport of ingested fat and poorly water-soluble drugs through the intestinal mucous layer. METHODS: Sodium taurocholate (NaTC) was dispersed with egg phosphatidylcholines (PC) to yield mixed micelles of a specific size and concentration. A preliminary study was conducted to determine the time required for equilibration of PC/TC micellar solutions with mucin. PC/TC micellar solutions were dialyzed against fixed and variable concentrations of bovine submaxillary mucin after which the concentration of PC and NaTC was measured by an assay for total phosphorus and by HPLC, respectively. In addition, a quantitative assay of TC and PC by NMR was developed and used to estimate the mobile fraction of lipids in the samples. Finally, pulsed-field gradient spin echo NMR self-diffusion measurements were made of the water, TC, and PC in the samples obtained from dialysis. RESULTS: TC/PC micellar solutions achieved equilibrium with mucin in 7 days. Mucin did not affect the equilibrium concentration of PC or TC, except at high concentrations of mucin (5%), and then the effect was small. NMR quantitation was valid for PC and TC systems containing small micelles, but deviated significantly with systems containing large micelles. Mucin decreased the diffusivity of water and the phospholipids, but the effect was relatively small. Mucin dramatically affected the mobility of TC, which prevented a straightforward interpretation of the calculated diffusion coefficients. CONCLUSIONS: Mucin has a minor effect on the equilibrium distribution of phospholipids and bile salts. However, lipids are readily accommodated by mucus, which can significantly increase the permeability of the mucous layer, particularly for poorly water-soluble drugs.
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