Acosta Edgar J, Policova Zdenka, Lee Simon, Dang Andrew, Hair Michael L, Neumann A Wilhelm
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON M5S3E5, Canada.
Biochim Biophys Acta. 2010 May;1798(5):882-90. doi: 10.1016/j.bbamem.2010.01.017. Epub 2010 Feb 6.
Chitosan, a cationic polysaccharide, has been found to improve the surface activity of lung surfactant extracts in the presence of various inhibitors. It has been proposed that chitosan binds to anionic lipids (e.g. phosphatidyl glycerols) in lung surfactants, producing stable lipid films at the air-water interface. This binding also reverses the net charge of the surfactant aggregates, from negative to positive. Unfortunately, positively charged aggregates may adsorb or interact with the negatively charged epithelial tissue, leading to poor surfactant performance. To address this issue an anionic polysaccharide, dextran sulfate (dexS), was used as a secondary coating to reverse the charge of chitosan-lung surfactant extracts without affecting the surface activity of the preparation. The dynamic surface tension and zeta potential of bovine lipid extract surfactant (BLES) containing chitosan chloride (chiCl) and dexS were evaluated as a function of dexS concentration. These studies were conducted in the absence and presence of sodium bicarbonate buffer, and in the absence and presence of bovine serum used as model inhibitor. It was determined that using an appropriate concentration of dexS, especially at physiological pH, it is possible to restore the negative charge of the surfactant aggregates, and retain their surface activity, even in the presence of bovine serum. High concentrations of dexS affect the binding of chiCl to BLES, and the surface activity of the preparation.
壳聚糖是一种阳离子多糖,已发现在存在各种抑制剂的情况下,它能提高肺表面活性剂提取物的表面活性。有人提出,壳聚糖与肺表面活性剂中的阴离子脂质(如磷脂酰甘油)结合,在气-水界面形成稳定的脂质膜。这种结合还会使表面活性剂聚集体的净电荷从负变为正。不幸的是,带正电荷的聚集体可能会吸附或与带负电荷的上皮组织相互作用,导致表面活性剂性能不佳。为了解决这个问题,一种阴离子多糖硫酸葡聚糖(dexS)被用作二次涂层,以逆转壳聚糖-肺表面活性剂提取物的电荷,而不影响制剂的表面活性。评估了含有壳聚糖氯化物(chiCl)和dexS的牛脂质提取物表面活性剂(BLES)的动态表面张力和zeta电位随dexS浓度的变化。这些研究在有无碳酸氢钠缓冲液以及有无用作模型抑制剂的牛血清的情况下进行。结果表明,使用适当浓度的dexS,尤其是在生理pH值下,即使在存在牛血清的情况下,也有可能恢复表面活性剂聚集体的负电荷,并保持其表面活性。高浓度的dexS会影响chiCl与BLES的结合以及制剂的表面活性。