Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
Chem Biodivers. 2011 Dec;8(12):2195-210. doi: 10.1002/cbdv.201100097.
The interaction of amphiphilic molecules such as lipids and surfactants with the hydrophilic drug carboplatin was investigated to identify suitable self-assembling components for a potential gel-based delivery formulation. (1) H-NMR Studies in sodium bis(2-ethylhexyl) sulfosuccinate (aerosol-OT, AOT)-based reverse micelles show that carboplatin associates and at least partially penetrates the surfactant interface. Langmuir monolayers formed by dipalmitoyl(phosphatidyl)choline are penetrated by carboplatin. Carboplatin was found to also penetrate the more rigid monolayers containing cholesterol. A combined mixed surfactant gel formulation containing carboplatin and cholesterol for lymphatic tissue targeting was investigated for the intracavitary treatment of cancer. This formulation consists of a blend of the surfactants lecithin and AOT (1 : 3 ratio), an oil phase of isopropyl myristate, and an aqueous component. The phases of the system were defined within a pseudo-ternary phase diagram. At low oil content, this formulation produces a gel-like system over a wide range of H(2) O content. The carboplatin release from the formulation displays a prolonged discharge with a rate three to five times slower than that of the control. Rheological properties of the formulation exhibit pseudoplastic behavior. Microemulsion and Langmuir monolayer studies support the interactions between carboplatin and amphiphilic components used in this formulation. To target delivery of carboplatin, two formulations containing cholesterol were characterized. These two formulations with cholesterol showed that, although cholesterol does little to alter the phases in the pseudo-ternary system or to increase the initial release of the drug, it contributes significantly to the structure of the formulation under physiological temperature, as well as increases the rate of steady-state discharge of carboplatin.
研究了两亲分子（如脂质和表面活性剂）与亲水性药物卡铂的相互作用，以确定适用于潜在基于凝胶的递药制剂的自组装成分。（1）在基于双（2-乙基己基）磺基琥珀酸钠（AOT，气溶胶-OT）的反胶束中进行的 1 H-NMR 研究表明，卡铂与表面活性剂相互作用并至少部分穿透其界面。二棕榈酰（磷脂酰）胆碱形成的 Langmuir 单层被卡铂穿透。发现卡铂也穿透含有胆固醇的更刚性单层。研究了包含卡铂和胆固醇的混合表面活性剂凝胶制剂用于淋巴组织靶向，以用于腔内癌症治疗。该制剂由卵磷脂和 AOT（1：3 比例）的混合表面活性剂、肉豆蔻酸异丙酯油相和水相组成。在假三元相图中定义了该系统的相。在低油含量下，该制剂在较宽的 H 2 O 含量范围内产生凝胶状系统。制剂中卡铂的释放显示出延长的释放，其释放速率比对照慢三到五倍。制剂的流变性质表现出假塑性行为。微乳液和 Langmuir 单层研究支持卡铂与该制剂中使用的两亲性成分之间的相互作用。为了靶向卡铂的递药，对两种含有胆固醇的制剂进行了表征。这两种含有胆固醇的制剂表明，尽管胆固醇对假性三元体系中的相变化或增加药物的初始释放影响不大，但它对生理温度下制剂的结构有显著贡献，并增加了卡铂的稳态释放速率。
