Self-assembly of the beta blocker, propranolol hydrochloride under physiological conditions

Some drug molecules are surface active and, as such, self-assemble into micellar structures when present above a concentration known as their critical micelle concentration (cmc), although there is evidence of pre-micellar aggregation with some drugs. What is not currently understood is whether this “surfactant-like” behaviour is important for the drug's therapeutic activity. As part of a larger study aimed at gaining insight into the structure-function relationship between a drug’s surface active nature and its therapeutic activity, we wish to perform contrast variation SANS experiments in order to understand how the conditions that the drug would encounter in the body might influence its aggregation behaviour. The results of this study will be combined with molecular dynamic studies.

部分药物分子具有表面活性，因此当其浓度高于临界胶束浓度（critical micelle concentration, cmc）时，会自组装形成胶束结构；不过已有研究证据显示，部分药物会出现胶束前聚集现象。目前尚未明确的是，这种“表面活性剂样”行为是否对药物的治疗活性具有重要意义。作为一项旨在阐明药物表面活性特性与其治疗活性之间构效关系的大型研究的组成部分，本研究拟开展对比度变化小角中子散射（Small-Angle Neutron Scattering, SANS）实验，以探究药物在体内所遭遇的环境条件如何影响其聚集行为。本研究的结果将与分子动力学（Molecular Dynamics, MD）研究相结合。