Sethy Dasaratha, Chakraborty Hirak
School of Chemistry, Sambalpur University, Burla, Odisha 768 019, India.
School of Chemistry, Sambalpur University, Burla, Odisha 768 019, India.
Chem Phys Lipids. 2016 Oct;200:120-125. doi: 10.1016/j.chemphyslip.2016.09.001. Epub 2016 Sep 25.
The interfacial properties of the membrane are exceptionally vital in drug-membrane interaction. They not only select out a particular prototropic form of the drug molecule for incorporation, but are also potent enough to induce structural switchover of these drugs in several cases. In this work, we quantitatively monitored the change in dipolar rearrangement of the micellar interface (as a simplified membrane mimic) by measuring the dielectric constant and dipole potential with the micellization of SDS at pH 3.6. The dielectric constant and dipole potential were measured utilizing the fluorescence of polarity sensitive probe, pyrene and potential-sensitive probe, di-8-ANEPPS, respectively. Our study demonstrates that the change in dipolar rearrangement directly influences the switchover equilibrium between the anionic and neutral from of piroxicam. We have further extended our work to evaluate the effect of hydrophobic chain length of the surfactants on the dipolar rearrangement and its effect on the structural switchover of piroxicam. It is interesting that the extent of switchover of piroxicam is directly correlated with the dipolar rearrangement induced bythe varying hydrophobic chain length of the surfactants. To the best of our knowledge, our results constitute the first report to show the dependence of dipole potential on the hydrophobic chain length of the surfactant and demonstrate that the dipolar rearrangement directly tunes the extent of structural switchover of piroxicam, which was so far only intuitive. We consider that this new finding would have promising implication in drug distribution and drug efficacy.
膜的界面性质在药物与膜的相互作用中极其重要。它们不仅会选择特定的质子型药物分子进行包合，而且在某些情况下还足以促使这些药物发生结构转变。在这项工作中，我们通过在pH 3.6条件下测量SDS胶束化过程中的介电常数和偶极电势，定量监测了胶束界面（作为简化的膜模拟物）偶极重排的变化。介电常数和偶极电势分别利用极性敏感探针芘的荧光和电势敏感探针di-8-ANEPPS进行测量。我们的研究表明，偶极重排的变化直接影响吡罗昔康阴离子型和中性型之间的转变平衡。我们进一步拓展工作，评估表面活性剂疏水链长度对偶极重排的影响及其对吡罗昔康结构转变的作用。有趣的是，吡罗昔康的转变程度与表面活性剂不同疏水链长度引起的偶极重排直接相关。据我们所知，我们的结果首次表明偶极电势对表面活性剂疏水链长度的依赖性，并证明偶极重排直接调节吡罗昔康的结构转变程度，而这一点迄今为止只是凭直觉。我们认为这一新发现将对药物分布和药效产生有前景的影响。
