Manrique-Moreno Marcela, Garidel Patrick, Suwalsky Mario, Howe Jörg, Brandenburg Klaus
Instituto de Química, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, A.A. 1226, Medellín, Colombia.
Biochim Biophys Acta. 2009 Jun;1788(6):1296-303. doi: 10.1016/j.bbamem.2009.01.016. Epub 2009 Feb 6.
Nonsteroidal anti-inflammatory drugs (NSAIDs) represent non-specific inhibitors of the cycloxygenase pathway of inflammation, and therefore an understanding of the interaction process of the drugs with membrane phospholipids is of high relevance. We have studied the interaction of the NSAIDs with phospholipid membranes made from dimyristoylphosphatidylcholine (DMPC) by applying Fourier-transform infrared spectroscopy (FTIR), Förster resonance energy transfer spectroscopy (FRET), differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC). FTIR data obtained via attenuated total reflectance (ATR) show that the interaction between DMPC and NSAIDs is limited to a strong interaction of the drugs with the phosphate region of the lipid head group. The FTIR transmission data furthermore are indicative of a strong effect of the drugs on the hydrocarbon chains inducing a reduction of the chain-chain interactions, i.e., a fluidization effect. Parallel to this, from the DSC data beside the decrease of T(m) a reduction of the peak height of the melting endotherm connected with its broadening is observed, but leaving the overall phase transition enthalpy constant. Additionally, phase separation is observed, inducing the formation of a NSAID-rich and a NSAID-poor phase. This is especially pronounced for Diclofenac. Despite the strong influence of the drugs on the acyl chain moiety, FRET data do not reveal any evidence for drug incorporation into the lipid matrix, and ITC measurements performed do not exhibit any heat production due to drug binding. This implies that the interaction process is governed by only entropic reactions at the lipid/water interface.
非甾体抗炎药（NSAIDs）是炎症环氧化酶途径的非特异性抑制剂，因此了解这些药物与膜磷脂的相互作用过程具有高度相关性。我们通过应用傅里叶变换红外光谱（FTIR）、Förster共振能量转移光谱（FRET）、差示扫描量热法（DSC）和等温滴定量热法（ITC），研究了NSAIDs与由二肉豆蔻酰磷脂酰胆碱（DMPC）制成的磷脂膜的相互作用。通过衰减全反射（ATR）获得的FTIR数据表明，DMPC与NSAIDs之间的相互作用仅限于药物与脂质头部基团的磷酸区域的强相互作用。此外，FTIR透射数据表明药物对烃链有强烈影响，导致链间相互作用减少，即流化效应。与此同时，从DSC数据中可以观察到，除了Tm降低外，与熔解吸热峰高度降低及其变宽相关，但总相变焓保持不变。此外，还观察到相分离，导致形成富含NSAID和贫NSAID的相。这在双氯芬酸中尤为明显。尽管药物对酰基链部分有强烈影响，但FRET数据并未揭示药物掺入脂质基质的任何证据，并且进行的ITC测量未显示由于药物结合而产生的任何热量。这意味着相互作用过程仅由脂质/水界面处的熵反应控制。
