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Diffusivity of bile salt/phospholipid aggregates in mucin
C Y Li1, C L Zimmerman, T S Wiedmann
1Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
Purpose:
The objective of this study is to evaluate the effect of the mucous layer on the transport of the drug-solubilizing bile salt/phosphatidylcholine (BS/PC) aggregates.
Methods:
The self-diffusion coefficient of BS/PC aggregates in bovine submaxillary mucin (BSM) was measured by Fourier-transform pulsed-field gradient spin-echo (FT-PGSE) 1H NMR spectroscopy.
Results:
In spite of the complexity of the mixture, the FT-PGSE technique allowed the unambiguous determination of the diffusivity of PC and 1H2HO (HDO, natural abundance in D2O). With a series of BS/PC total lipid concentrations ranging from 1 to 7 g/dl, a progressive decrease in the effective diffusivity of HDO was observed with an increase in the both the BSM and total lipid concentration. The effective diffusivity of PC decreased with increasing lipid concentrations in the presence of mucin, while in the controls it increased. After correcting the effective diffusivity of PC for the obstruction effect of mucin, the size of the BS/PC mixed micelle was assessed. It appears that PC associates with BSM resulting in a decrease in the available PC for micellization. This reduces the average size of the mixed micelle within the mucous layer.
Conclusions:
The aggregation state of BS/PC micelle is altered by the presence of mucin which would have a direct impact on the transport of dietary lipid and solubilized drug through the aqueous boundary layer of the intestinal tract.