title: Water-soluble dendritic core-shell-type architectures based on polyglycerol for solubilization of hydrophobic drugs.
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.
authors.affiliation: Organic Polymer Chemistry, Department of Chemistry, University of Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Türk
authors.forename: Anuj
authors.initials: A
authors.lastname: Shukla
authors.forename: Paula Cristina
authors.initials: PC
authors.lastname: Alves Rodrigues
authors.forename: Heinz
authors.initials: H
authors.lastname: Rehage
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D016503:Drug Delivery Systems; D005990:Glycerol / Q000138:chemical synthesis* / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009553:Nimodipine / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D011721:Pyrenes / Q000737:chemistry; D012995:Solubility
chemical_list: D050091:Dendrimers; D011108:Polymers; D011721:Pyrenes; C043941:polyglycerol; D009553:Nimodipine; C030984:pyrene; D005990:Glycerol