Alsop Richard J, Armstrong Clare L, Maqbool Amna, Toppozini Laura, Dies Hannah, Rheinstädter Maikel C
Department of Physics and Astronomy, McMaster University, ABB-241, 1280 Main Street West, Hamilton, Ontario L8S 4M1, Canada.
Soft Matter. 2015 Jun 28;11(24):4756-67. doi: 10.1039/c5sm00597c. Epub 2015 Apr 27.
There is increasing evidence that common drugs, such as aspirin and ibuprofen, interact with lipid membranes. Ibuprofen is one of the most common over the counter drugs in the world, and is used for relief of pain and fever. It interacts with the cyclooxygenase pathway leading to inhibition of prostaglandin synthesis. From X-ray diffraction of highly oriented model membranes containing between 0 and 20 mol% ibuprofen, 20 mol% cholesterol, and dimyristoylphosphatidylcholine (DMPC), we present evidence for a non-specific interaction between ibuprofen and cholesterol in lipid bilayers. At a low ibuprofen concentrations of 2 mol%, three different populations of ibuprofen molecules were found: two in the lipid head group region and one in the hydrophobic membrane core. At higher ibuprofen concentrations of 10 and 20 mol%, the lamellar bilayer structure is disrupted and a lamellar to cubic phase transition was observed. In the presence of 20 mol% cholesterol, ibuprofen (at 5 mol%) was found to be expelled from the membrane core and reside solely in the head group region of the bilayers. 20 mol% cholesterol was found to stabilize lamellar membrane structure and the formation of a cubic phase at 10 and 20 mol% ibuprofen was suppressed. The results demonstrate that ibuprofen interacts with lipid membranes and that the interaction is strongly dependent on the presence of cholesterol.
越来越多的证据表明，阿司匹林和布洛芬等常见药物会与脂质膜相互作用。布洛芬是世界上最常见的非处方药之一，用于缓解疼痛和退烧。它与环氧化酶途径相互作用，导致前列腺素合成受到抑制。通过对含有0至20摩尔%布洛芬、20摩尔%胆固醇和二肉豆蔻酰磷脂酰胆碱（DMPC）的高度取向模型膜进行X射线衍射，我们提供了布洛芬与脂质双层中胆固醇之间非特异性相互作用的证据。在布洛芬浓度为2摩尔%的低浓度下，发现了三种不同的布洛芬分子群体：两种在脂质头部基团区域，一种在疏水膜核心。在布洛芬浓度为10和20摩尔%的较高浓度下，层状双层结构被破坏，观察到层状向立方相的转变。在存在20摩尔%胆固醇的情况下，发现布洛芬（5摩尔%）从膜核心被排出，仅存在于双层的头部基团区域。发现20摩尔%胆固醇可稳定层状膜结构，并抑制在10和20摩尔%布洛芬时立方相的形成。结果表明布洛芬与脂质膜相互作用，且这种相互作用强烈依赖于胆固醇的存在。
