Ramírez Patricio, Alcaraz Antonio, Mafé Salvador, Pellicer Julio
Departament de Física Aplicada, Universitat Politècnica de València, Camino de Vera s/n, València, E-46022, Spain.
J Colloid Interface Sci. 2002 Sep 1;253(1):171-9. doi: 10.1006/jcis.2002.8508.
We have studied theoretically the partition equilibrium of a cationic drug between an electrolyte solution and a membrane with pH-dependent fixed charges using an extended Donnan formalism. The aqueous solution within the fixed charge membrane is assumed to be in equilibrium with an external aqueous solution containing six ionic species: the cationic drug (DH(+)), the salt cations (Na(+) and Ca(2+)), the salt anion (Cl(-)), and the hydrogen and hydroxide ions. In addition to these mobile species, the membrane solution may also contain four fixed species attached to the membrane chains: strongly acid sulfonic groups (SO(3)(-)), weakly acid carboxylic groups in dissociated (COO(-)) and neutral (COOH) forms, and positively charged groups (COO...Ca(+)) resulting from Ca(2+) binding to dissociated weakly acid groups. The ionization state of the weak electrolyte groups attached to the membrane chains is analyzed as a function of the local pH, salt concentration, and drug concentration in the membrane solution, and particular attention is paid to the effects of the Ca(2+) binding to the negatively charged membrane fixed groups. The lipophilicity of the drug is simulated by the chemical partition coefficient between the membrane and external solutions giving the tendency of the drug to enter the membrane solution due to hydrophobic interactions. Comparison of the theoretical results with available experimental data allows us to explain qualitatively the effects that the pH, salt concentration, drug concentration, membrane fixed charge concentration, and Ca(2+) binding exert on the ionic drug equilibrium. The role of the interfacial (Donnan) electric potential difference between the membrane and the external solutions on this ionic drug equilibrium is emphasized throughout the paper.
我们使用扩展的唐南形式理论研究了阳离子药物在电解质溶液和具有pH依赖性固定电荷的膜之间的分配平衡。假设固定电荷膜内的水溶液与含有六种离子物种的外部水溶液处于平衡状态：阳离子药物（DH(+)）、盐阳离子（Na(+)和Ca(2+)）、盐阴离子（Cl(-)）以及氢离子和氢氧根离子。除了这些可移动物种外，膜溶液还可能包含附着在膜链上的四种固定物种：强酸磺酸基团（SO(3)(-)）、解离形式（COO(-)）和中性形式（COOH）的弱酸羧酸基团，以及Ca(2+)与解离的弱酸基团结合产生的带正电基团（COO...Ca(+)）。分析了附着在膜链上的弱电解质基团的电离状态与膜溶液中局部pH、盐浓度和药物浓度的函数关系，并特别关注Ca(2+)与带负电的膜固定基团结合的影响。通过膜与外部溶液之间的化学分配系数模拟药物的亲脂性，该系数反映了药物由于疏水相互作用进入膜溶液的倾向。将理论结果与现有实验数据进行比较，使我们能够定性地解释pH、盐浓度、药物浓度、膜固定电荷浓度和Ca(2+)结合对离子药物平衡的影响。本文始终强调膜与外部溶液之间的界面（唐南）电势差对这种离子药物平衡的作用。
