Thermodynamics of Indomethacin Adsorption to Phospholipid Membranes,The Journal of Physical Chemistry B

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Thermodynamics of Indomethacin Adsorption to Phospholipid Membranes
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2017-11-09 00:00:00 , DOI: 10.1021/acs.jpcb.7b08359
Amanda D. Fearon ₁ , Grace Y. Stokes ₁

Affiliation

Using second-harmonic generation, we directly monitored adsorption of indomethacin, a nonsteroidal anti-inflammatory drug, to supported lipid bilayers composed of phospholipids of varying phase, cholesterol content, and head group charge without the use of extrinsic labels at therapeutically relevant aqueous concentrations. Indomethacin adsorbed to gel-phase lipids with a high binding affinity, suggesting that like other arylacetic acid-containing drugs, it preferentially interacts with ordered lipid domains. We discovered that adsorption of indomethacin to gel-phase phospholipids was endothermic and entropically driven, whereas adsorption to fluid-phase phospholipids was exothermic and enthalpically driven. As temperature increased from 19 to 34 °C, binding affinities to gel-phase lipids increased by 7-fold but relative surface concentration decreased to one-fifth of the original value. We also compared our results to the entropies reported for indomethacin adsorbed to surfactant micelles, which are used in drug delivery systems, and assert that adsorbed water molecules in the phospholipid bilayer may be buried deeper into the acyl chains and less accessible for disruption. The thermodynamic studies reported here provide mechanistic insight into indomethacin interactions with mammalian plasma membranes in the gastrointestinal tract and inform studies of drug delivery, where indomethacin is commonly used as a prototypical, hydrophobic small-molecule drug.

中文翻译：

吲哚美辛吸附磷脂膜的热力学

使用第二谐波产生器，我们直接监测了吲哚美辛（一种非甾体类抗炎药）在支持的脂质双层上的吸附情况，该脂质双层由不同相的磷脂，胆固醇含量和头部基团电荷组成，而在治疗相关的水浓度下无需使用外源性标记。消炎痛以高结合亲和力吸附到凝胶相脂质上，表明与其他含芳基乳酸的药物一样，它优先与有序脂质域相互作用。我们发现消炎痛对凝胶相磷脂的吸附是吸热和熵驱动的，而对液相磷脂的吸附则是放热和焓驱动的。随着温度从19°C上升到34°C，与凝胶相脂质的结合亲和力增加了7倍，但相对表面浓度却降低到了原始值的五分之一。我们还将结果与报道的吲哚美辛吸附在表面活性剂胶束上的吲哚美辛进行了比较，吲哚美辛被用于药物输送系统，并断言磷脂双层中吸附的水分子可能更深地埋藏在酰基链中，难以被破坏。此处报道的热力学研究提供了对吲哚美辛与胃肠道中哺乳动物质膜相互作用的机制的了解，并为药物递送研究提供了信息，其中吲哚美辛通常用作原型疏水性小分子药物。我们还将结果与报道的吲哚美辛吸附在表面活性剂胶束上的吲哚美辛进行了比较，吲哚美辛被用于药物输送系统，并断言磷脂双层中吸附的水分子可能更深地埋藏在酰基链中，难以被破坏。此处报道的热力学研究提供了对吲哚美辛与胃肠道中哺乳动物质膜相互作用的机制的了解，并为药物递送研究提供了信息，其中吲哚美辛通常用作原型疏水性小分子药物。我们还将结果与报道的吲哚美辛吸附在表面活性剂胶束上的吲哚美辛进行了比较，吲哚美辛被用于药物输送系统，并断言磷脂双层中吸附的水分子可能更深地埋藏在酰基链中，难以被破坏。此处报道的热力学研究提供了吲哚美辛与胃肠道中哺乳动物质膜相互作用的机械原理，并为药物递送研究提供了信息，其中吲哚美辛通常用作原型疏水性小分子药物。

更新日期：2017-11-09

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