REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Pharm Res. 2013 Aug;30(8):2097-107. doi: 10.1007/s11095-013-1066-8. Epub 2013 May 24.
To study interactions between nonsteroidal anti-inflammatory drugs (NSAIDs) and membrane mimetic models.
The interactions of indomethacin and nimesulide with liposomes of dipalmitoylphosphatidylcholine (DPPC) at two physiological pH conditions (pH 7.4 and 5.0) were investigated by time-resolved and steady-state fluorescence techniques and derivative ultraviolet/visible absorption spectrophotometry. Fluorescence quenching studies that assess the location of the drugs interacting with the membrane were carried out using labeled liposomes with trimethylammonium-diphenylhexatriene (TMA-DPH), a fluorescent probe with well-known membrane localization. Partition of the drugs within membranes was determined by calculating their partition coefficients (K p ) between liposomes and water using derivative ultraviolet/visible absorption spectrophotometry in a temperature range of 37-50°C. The Van't Hoff analysis of the temperature dependence of K p values allowed calculating the membrane-water variation of enthalpy (ΔH w→m) and entropy (ΔS w→m) and consequently the Gibbs free energy (ΔG w→m).
Results indicate that quenching, partitioning and thermodynamic parameters inherent to the interaction of the studied drugs with the membrane mimetic model are deeply dependent on the initial organization of the membrane, on the pH medium and on the physical properties of the drug.
The interactions between NSAIDs and membranes are manifested as changes in the physical and thermodynamic properties of the bilayers. Depending on the composition and physical state of the membrane and the chemical structure of the NSAID, the interaction can support or prevent drug activity or toxicity.
研究非甾体抗炎药（NSAIDs）与膜模拟模型之间的相互作用。
采用时间分辨和稳态荧光技术以及导数紫外可见吸收分光光度法研究了吲哚美辛和尼美舒利在两种生理 pH 值条件（pH 7.4 和 5.0）下与二棕榈酰磷脂酰胆碱（DPPC）脂质体的相互作用。荧光猝灭研究使用具有明确膜定位的荧光探针三甲基铵-二苯基己三烯（TMA-DPH）标记的脂质体评估药物与膜相互作用的位置。通过在 37-50°C 的温度范围内使用导数紫外可见吸收分光光度法计算药物在脂质体和水中的分配系数（Kp），确定药物在膜内的分配。Van't Hoff 分析 Kp 值随温度的变化，允许计算膜-水之间焓（ΔHw→m）和熵（ΔSw→m）的变化，从而得到吉布斯自由能（ΔGw→m）。
结果表明，所研究药物与膜模拟模型相互作用的猝灭、分配和热力学参数严重依赖于膜的初始组织、pH 介质和药物的物理性质。
NSAIDs 与膜之间的相互作用表现为双层物理和热力学性质的变化。取决于膜的组成和物理状态以及 NSAID 的化学结构，相互作用可以支持或阻止药物的活性或毒性。
