Kubo M, Gardner M F, Hostetler K Y
Biochem Pharmacol. 1986 Nov 1;35(21):3761-5. doi: 10.1016/0006-2952(86)90662-3.
Binding of propranolol and gentamicin to small unilamellar phospholipid vesicles having different surface charges was studied at pH 4.4 using an ultra-centrifugation method, and the results were analyzed by an equation describing the Langmuir adsorption isotherms. Gentamicin, a polycationic drug, bound to negatively-charged small unilamellar vesicles composed of 60% phosphatidylcholine and 40% of either phosphatidylinositol, phosphatidylglycerol or phosphatidylserine in a manner consistent with a single class of binding sites but did not bind at all to small unilamellar vesicles of phosphatidylcholine alone. In contrast, propranolol bound readily to both neutral and negatively-charged liposomes in a manner consistent with two types of binding sites. Based on the binding parameters calculated from replots, it is suggested that the high-affinity site is probably at the surface of the liposome and that ionic forces are primarily responsible for this binding. The low-affinity, high-capacity binding site for propranolol was demonstrated with both neutral and negatively-charged liposomes and appeared to be independent of the surface charge. Gentamicin, which is not hydrophobic, did not bind to the low-affinity site. It is hypothesized that hydrophobic interactions are the driving force for propranolol binding to the low-affinity site which may be the interior of the lipid bilayer.
在pH 4.4条件下，采用超速离心法研究了普萘洛尔和庆大霉素与具有不同表面电荷的小单层磷脂囊泡的结合情况，并通过描述朗缪尔吸附等温线的方程对结果进行了分析。庆大霉素是一种聚阳离子药物，它以与单一类结合位点一致的方式与由60%磷脂酰胆碱和40%磷脂酰肌醇、磷脂酰甘油或磷脂酰丝氨酸组成的带负电荷的小单层囊泡结合，但完全不与仅由磷脂酰胆碱组成的小单层囊泡结合。相比之下，普萘洛尔以与两种类型结合位点一致的方式很容易与中性和带负电荷的脂质体结合。根据从重新绘制的图中计算出的结合参数，表明高亲和力位点可能在脂质体表面，并且离子力是这种结合的主要原因。普萘洛尔的低亲和力、高容量结合位点在中性和带负电荷的脂质体中均得到证实，并且似乎与表面电荷无关。庆大霉素不具有疏水性，不与低亲和力位点结合。据推测，疏水相互作用是普萘洛尔与低亲和力位点结合的驱动力，该位点可能是脂质双层的内部。
