Barwicz J, Gareau R, Audet A, Morisset A, Villiard J, Gruda I
Département de chimie-biologie, Université du Québec à Trois-Rivières, Canada.
Biochem Biophys Res Commun. 1991 Dec 16;181(2):722-8. doi: 10.1016/0006-291x(91)91250-g.
Amphotericin B (AmB) is a potent antifungal agent used to treat patients with systemic mycoses. The clinical usefulness of the drug is limited by its high toxicity and several new less toxic formulations of AmB have been recently developed. In order to understand the mechanism of the decreases of toxicity caused by various new delivery systems, we have investigated by uv-visible spectroscopy the interaction of two of these formulations with human blood lipoproteins. The results were compared with those obtained with the commonly used pharmaceutical form of AmB (Fungizone). This study shows that AmB-lipoprotein interaction is hindered when the drug is in a monomeric form and/or when it is included in phospholipid-surfactant micelles. In an in vivo study on mice it is shown here that AmB monomerized by surfactant is less toxic to animals than the same concentration of Fungizone, where the polyene is strongly aggregated. It may be concluded from the present study that the AmB species which is responsible for the in vivo toxicity is a complex of the antibiotic with the low density and the very low density blood lipoproteins and that hindering of this complex formation results in a decrease of AmB toxicity.
两性霉素B（AmB）是一种用于治疗系统性真菌病患者的强效抗真菌剂。该药物的临床应用因高毒性而受限，最近已开发出几种毒性较低的新型两性霉素B制剂。为了了解各种新型给药系统导致毒性降低的机制，我们通过紫外可见光谱法研究了其中两种制剂与人类血液脂蛋白的相互作用。将结果与使用常用剂型两性霉素B（注射用两性霉素B）所获得的结果进行了比较。这项研究表明，当药物呈单体形式和/或包含在磷脂 - 表面活性剂胶束中时，两性霉素B与脂蛋白的相互作用会受到阻碍。在此进行的一项对小鼠的体内研究表明，由表面活性剂单体化的两性霉素B对动物的毒性低于相同浓度的注射用两性霉素B，在后者中多烯强烈聚集。从本研究可以得出结论，导致体内毒性的两性霉素B种类是抗生素与低密度和极低密度血液脂蛋白的复合物，并且这种复合物形成的受阻导致两性霉素B毒性降低。
