Water‐Soluble Dendritic Core–Shell‐Type Architectures Based on Polyglycerol for Solubilization of Hydrophobic Drugs

Since many potential drugs are poorly water soluble, there is a high demand for solubilization agents. Here, we describe the synthesis of dendritic core–shell‐type architectures based on hyperbranched polyglycerol for the solubilization of hydrophobic drugs. Amphiphilic macromolecules containing hydrophobic biphenyl groups in the core were synthesized in an efficient three‐ or four‐step procedure by employing Suzuki‐coupling reactions. These species were then used to solubilize the commercial drug nimodipine, a calcium antagonist used for the treatment of heart diseases and neurological deficits. Pyrene was also used as a hydrophobic model compound. It turned out that the transport properties of the dendritic polyglycerol derivatives, which are based on hydrophobic host–guest interactions, depend strongly on the degree and type of core functionalization. In the case of the multifunctional nimodipine, additional specific polymer–drug interactions could be tailored by this flexible core design, as detected by UV spectroscopy. The enhancement of solubilization increased 300‐fold for nimodipine and 6000‐fold for pyrene at a polymer concentration of 10 wt %. The sizes of the polymer–drug complexes were determined by both dynamic light scattering (DLS) experiments and transmission electron microscopy (TEM), and extremely well‐defined aggregates with diameters of approximately 10 nm in the presence of a drug were observed. These findings together with a low critical aggregate concentration of 4×10 −6  mol L −1 indicate the controlled self‐assembly of the presented amphiphilic dendritic core–shell‐type architectures rather than a unimolecular transport behavior.