Photocleavable core cross-linked polymeric micelles of polypept(o)ides and ruthenium(II) complexes

Core cross-linking of polymeric micelles has been demonstrated to contribute to enhanced stability that can improve the therapeutic efficacy. Photochemistry has the potential to provide spatial resolution and on-demand drug release. In this study, light-sensitive polypyridyl-ruthenium(II) complexes were combined with polypept(o)ides for photocleavable core cross-linked polymeric micelles. Block copolymers of polysarcosine-block-poly(glutamic acid) were synthesized by ring-opening N-carboxyanhydride polymerization and modified with aromatic nitrile-groups on the glutamic acid side chain. The modified copolymers self-assembled into micelles and were cross-linked by cis-diaquabis(2,2'-bipyridine)-ruthenium(II) ([Ru(bpy)2(H2O)2]2+) or cis-diaquabis(2,2'-biquinoline)-ruthenium(II) ([Ru(biq)2(H2O)2]2+). Depending on the flexibility and hydrophobicity of the nitrile linker, either small spherical structures (Dh 45 nm, PDI 0.11) or worm-like micelles were obtained. The cross-linking reaction did not affect the overall size distribution but induced a change in the metal-to-ligand charge transfer peak from 482 to 420 nm and 592 to 548 nm. The cross-linked micelles displayed colloidal stability after incubation with human blood plasma and during gel permeation chromatography in hexafluoroisopropanol. Light-induced cleavage of [Ru(bpy)2(H2O)2]2+ was accomplished within 300 s, while [Ru(biq)2(H2O)2]2+ could not be completely released. Analysis in HuH-7 cells revealed increased cytotoxicity via micellar delivery of [Ru(bpy)2(H2O)2]2+ but mostly irradiation damage for [Ru(biq)2(H2O)2]2+. Further evaluation in ovo confirmed stable circulation pointing towards the future development of quick-release complexes.Drug Delivery Technolog

Entwicklung von Technologien zur Verwertung industrieller Rueckstaende. T. 1 und T. 2 Verbrennung von PCB-haltigen Altoelen und Abfaellen in der zirkulierenden Wirbelschicht. Thermische Behandlung kontaminierter Boeden

The first part of the integrated research project will describe the effectual combination of PCD-containing waste oils in the CFB. A complete destruction of the organic material will be succeeded at temperatures above 800 C without production of concentrations of PCDD and PCDF having an negative influence to the environment. In the second part of the integrated research project a process of thermal treatment of organic contaminated soil in a rotary kiln with co-current flow and integrated afterburner will be presented. (orig.)Im 1. Teil des Vorhabens wird die erfolgreiche Verbrennung PCB-haltiger Altoele und Abfaellen in der zirkulierenden Wirbelschicht beschrieben und nachgewiesen, dass bei Temperaturen kurz oberhalb 800 C eine vollstaendige Zerstoerung der organischen Substanzen erfolgt und sich keine umweltrelevanten Konzentrationen an chlorierten Dioxinen und Furanen bilden. Im 2. Teil des Vorhabens wird ein Verfahren zur thermischen Behandlung organisch belasteter Boeden in einem Gleichstrom-Drehrohrofen mit integrierter Nachbrennkammer vorgestellt. (orig.)SIGLEAvailable from TIB Hannover: F93B1259+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman