Inhibition of intestinal absorption of cholesterol by surface-modified nanostructured aluminosilicate compounds

The aim of this work was to assess the ability of aqueous suspensions of surface-modified nanostructured aluminosilicate (NSAS) compounds to reduce the intestinal absorption of cholesterol in a rat model. The rats were divided into 10 treatment groups which included several NSAS compounds at various doses, ezetimibe at 10 mg/kg, stigmastanol at 50 mg/kg, and normal saline. All compounds and controls were independently administered by oral gavage and then a mixture of [3H]cholesterol and cold cholesterol in 10% Intralipid® was immediately administered orally to the animals. Systemic blood was sampled and the concentration of cholesterol in plasma was determined by means of radioactivity. Protonation of NSAS using an ion-exchange column resulted in significant inhibition of cholesterol absorption relative to the control group (31.5% and 38.6% reduction in absorption of cholesterol for 50 and 100 mg/kg doses, respectively). Other surface-ion modifications of NSAS compounds did not show significant effect on intestinal cholesterol absorption. The inhibition of cholesterol absorption by ezetimibe was superior and by stigmastanol was equal to the effect of protonated NSAS in the doses investigated in this study. In conclusion, protonated NSAS material seems to inhibit significantly the intestinal absorption of dietary cholesterol in a rat model. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2390-2400, 2009