Water-soluble dendritic core-shell-type architectures based on polyglycerol for solubilization of hydrophobic drugs

Chemistry. 2007;13(15):4187-96. doi: 10.1002/chem.200601337.

Abstract

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 4x10(-6) mol L-1 indicate the controlled self-assembly of the presented amphiphilic dendritic core-shell-type architectures rather than a unimolecular transport behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dendrimers / chemical synthesis*
  • Dendrimers / chemistry
  • Drug Delivery Systems*
  • Glycerol / chemical synthesis*
  • Glycerol / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Nimodipine / chemistry*
  • Polymers / chemical synthesis*
  • Polymers / chemistry
  • Pyrenes / chemistry
  • Solubility

Substances

  • Dendrimers
  • Polymers
  • Pyrenes
  • polyglycerol
  • Nimodipine
  • pyrene
  • Glycerol