Strategies to deliver drugs using nanocarriers, which are passively or actively targeted to their alleged site of action might favorably affect benefit–risk profiles of novel therapeutics. Here we tested the hypothesis whether the physico-chemical properties of the cargo as well as the actual conditions during encapsulation interfere during formulation of nanoparticular cargo–carrier systems. On the basis of previous work, a versatile class of nanocarriers is polyether-based ABC triblock terpolymer micelles with diameters below 50 nm. Their tunable chemistry and size allows to systematically vary important parameters. We demonstrate in vivo differences in pharmacokinetics and biodistribution not only dependent on micellar net charge but also on the properties of encapsulated (model) drugs and their localization within the micelles. On the basis of in vitro and in vivo evidence we propose that depending on drug cargo and encapsulation conditions micelles with homogeneous or heterogeneous corona structure are formed, contributing to an altered pharmacokinetic profile as differences in cargo location occur. Thus, these interactions have to be considered when a carrier system is selected to achieve optimal delivery to a given tissue.

使用纳米载体传递药物的策略可能被动或主动地针对其所谓的作用部位，可能会有利地影响新型疗法的获益风险。在这里，我们测试了以下假设：在纳米颗粒状载货系统的配制过程中，货物的物理化学性质以及封装过程中的实际条件是否会受到干扰。根据先前的工作，一类通用的纳米载体是直径小于50 nm的基于聚醚的ABC三嵌段三元共聚物胶束。它们的化学性质和大小可调，可以系统地改变重要参数。我们在体内证明药代动力学和生物分布的差异不仅取决于胶束净电荷，而且还取决于封装的（模型）药物的特性及其在胶束中的定位。根据体外和体内证据，我们建议根据药物货物和包封条件，形成具有均质或异质电晕结构的胶束，当货物位置发生差异时，这会导致药代动力学特性发生变化。因此，这些相互作用有当选择一个载波系统，以实现最佳递送到给定的组织加以考虑。