Gershkovich Pavel, Darlington Jerry, Sivak Olena, Constantinides Panayiotis P, Wasan Kishor M
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
J Pharm Sci. 2009 Jul;98(7):2390-400. doi: 10.1002/jps.21616.
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 [(3)H]cholesterol and cold cholesterol in 10% Intralipid(R) 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.
这项工作的目的是评估表面改性的纳米结构硅铝酸盐（NSAS）化合物水悬浮液在大鼠模型中降低胆固醇肠道吸收的能力。将大鼠分为10个治疗组，其中包括几种不同剂量的NSAS化合物、10 mg/kg的依泽替米贝、50 mg/kg的豆甾烷醇以及生理盐水。所有化合物和对照组均通过口服灌胃独立给药，然后立即向动物口服给予[(3)H]胆固醇和冷胆固醇在10%英脱利匹特（Intralipid®）中的混合物。采集全身血液样本，并通过放射性测定血浆中胆固醇的浓度。相对于对照组，使用离子交换柱对NSAS进行质子化导致胆固醇吸收受到显著抑制（50和100 mg/kg剂量的胆固醇吸收分别降低31.5%和38.6%）。NSAS化合物的其他表面离子修饰对肠道胆固醇吸收未显示出显著影响。在本研究中所研究的剂量下，依泽替米贝对胆固醇吸收的抑制作用优于质子化NSAS，而豆甾烷醇的抑制作用与质子化NSAS相当。总之，质子化NSAS物质似乎能在大鼠模型中显著抑制膳食胆固醇的肠道吸收。
