Pharmaceutical nanosuspensions are formed when drug crystals are suspended in aqueous media in the presence of stabilizers. This technology offers a convenient way to enhance the dissolution of poorly water-soluble drug compounds. The stabilizers exert their action through electrostatic or steric interactions, however, the molecular requirements of stabilizing agents have not been studied extensively. Here, four structurally related amphiphilic Janus-dendrimers were synthesized and screened to determine the roles of different macromolecular domains on the stabilization of drug crystals. Physical interaction and nanomilling experiments have substantiated that Janus-dendrimers with fourth generation hydrophilic dendrons were superior to third generation analogues and Poloxamer 188 in stabilizing indomethacin suspensions. Contact angle and surface plasmon resonance measurements support the hypothesis that Janus-dendrimers bind to indomethacin surfaces via hydrophobic interactions and that the number of hydrophobic alkyl tails determines the adsorption kinetics of the Janus-dendrimers. The results showed that amphiphilic Janus-dendrimers adsorb onto drug particles and thus can be used to provide steric stabilization against aggregation and recrystallization. The modular synthetic route for new amphiphilic Janus-dendrimers offers, thus, for the first time a versatile platform for stable general-use stabilizing agents of drug suspensions.

中文翻译：

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新一代两亲性Janus-Dendrimers作为药物悬浮液的稳定剂

当药物晶体在稳定剂存在下悬浮在水性介质中时，会形成药物纳米悬浮液。这项技术提供了一种方便的方法来增强水溶性差的药物化合物的溶解。稳定剂通过静电或空间相互作用发挥作用，但是，对稳定剂的分子要求尚未得到广泛研究。在这里，合成并筛选了四个结构相关的两亲性Janus-树状大分子，以确定不同的大分子结构域在药物晶体稳定中的作用。物理相互作用和纳米研磨实验证实，具有第四代亲水树突的Janus树状聚合物在稳定吲哚美辛悬浮液方面优于第三代类似物和Poloxamer 188。接触角和表面等离振子共振测量结果支持了Janus-树状大分子通过疏水相互作用与吲哚美辛表面结合以及疏水性烷基尾部数目决定Janus-树状大分子的吸附动力学的假说。结果表明，两亲性Janus-树枝状大分子吸附到药物颗粒上，因此可用于提供针对聚集和重结晶的空间稳定作用。因此，用于新型两亲性Janus-树状聚合物的模块化合成路线首次为稳定的通用药物稳定剂悬浮液提供了一个多功能平台。