Drug-Induced Dynamics of Bile Colloids,Langmuir

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Drug-Induced Dynamics of Bile Colloids
Langmuir ( IF 3.7 ) Pub Date : 2021-02-15 , DOI: 10.1021/acs.langmuir.0c02282
Simon Hanio ₁ , Jonas Schlauersbach ₁ , Bettina Lenz ₁ , Franziska Spiegel ₂ , Rainer A. Böckmann ₂ , Ralf Schweins ₃ , Ivo Nischang _{4,

5} , Ulrich S. Schubert _{4,

5} , Sebastian Endres ₆ , Ann-Christin Pöppler ₆ , Ferdinand P. Brandl ₇ , Theo M. Smit ₇ , Karl Kolter ₇ , Lorenz Meinel _{1,

8}

Affiliation

Bile colloids containing taurocholate and lecithin are essential for the solubilization of hydrophobic molecules including poorly water-soluble drugs such as Perphenazine. We detail the impact of Perphenazine concentrations on taurocholate/lecithin colloids using analytical ultracentrifugation, dynamic light scattering, small-angle neutron scattering, nuclear magnetic resonance spectroscopy, coarse-grained molecular dynamics simulations, and isothermal titration calorimetry. Perphenazine impacted colloidal molecular arrangement, structure, and binding thermodynamics in a concentration-dependent manner. At low concentration, Perphenazine was integrated into stable and large taurocholate/lecithin colloids and close to lecithin. Integration of Perphenazine into these colloids was exothermic. At higher Perphenazine concentration, the taurocholate/lecithin colloids had an approximately 5-fold reduction in apparent hydrodynamic size, heat release was less exothermic upon drug integration into the colloids, and Perphenazine interacted with both lecithin and taurocholate. In addition, Perphenazine induced a morphological transition from vesicles to wormlike micelles as indicated by neutron scattering. Despite these surprising colloidal dynamics, these natural colloids successfully ensured stable relative amounts of free Perphenazine throughout the entire drug concentration range tested here. Future studies are required to further detail these findings both on a molecular structural basis and in terms of in vivo relevance.

中文翻译：

胆汁胶体的药物诱导动力学

含有牛磺胆酸盐和卵磷脂的胆汁胶体对于溶解疏水性分子（包括难溶于水的药物，例如奋乃静）的必不可少的。我们使用分析超速离心，动态光散射，小角度中子散射，核磁共振波谱，粗粒分子动力学模拟和等温滴定量热法详细研究了奋乃静浓度对牛磺胆酸盐/卵磷脂胶体的影响。奋乃静以浓度依赖的方式影响胶体分子的排列，结构和结合热力学。在低浓度下，奋乃静被整合到稳定的大牛磺酸胆甾醇/卵磷脂胶体中，并接近于卵磷脂。奋乃静整合到这些胶体中是放热的。在较高的奋乃静浓度下，牛磺胆酸盐/卵磷脂胶体的表观流体动力学尺寸降低了约5倍，药物整合到胶体中时放热较少放热，并且奋乃静与卵磷脂和牛磺胆酸酯相互作用。另外，如中子散射所示，奋乃静诱导了从囊泡到蠕虫状胶束的形态转变。尽管有这些令人惊讶的胶体动力学特性，但这些天然胶体成功地确保了在此处测试的整个药物浓度范围内游离奋乃静的相对稳定量。需要进一步的研究以分子结构和体内相关性进一步详述这些发现。和奋乃静与卵磷脂和牛磺胆酸盐相互作用。另外，如中子散射所示，奋乃静诱导了从囊泡到蠕虫状胶束的形态转变。尽管有这些令人惊讶的胶体动力学特性，但这些天然胶体成功地确保了在此处测试的整个药物浓度范围内游离奋乃静的相对稳定量。需要进一步的研究以分子结构和体内相关性进一步详述这些发现。和奋乃静与卵磷脂和牛磺胆酸盐相互作用。另外，如中子散射所示，奋乃静诱导了从囊泡到蠕虫状胶束的形态转变。尽管有这些令人惊讶的胶体动力学特性，但这些天然胶体成功地确保了在此处测试的整个药物浓度范围内游离奋乃静的相对稳定量。需要进一步的研究以分子结构和体内相关性进一步详述这些发现。这些天然胶体成功地确保了在此处测试的整个药物浓度范围内游离奋乃静的相对稳定量。需要进一步的研究以分子结构和体内相关性进一步详述这些发现。这些天然胶体成功地确保了在此处测试的整个药物浓度范围内游离奋乃静的相对稳定量。需要进一步的研究以分子结构和体内相关性进一步详述这些发现。

更新日期：2021-03-02

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