Biodegradable pH-sensitive polyurethane micelles with different polyethylene glycol (PEG) locations for anti-cancer drug carrier applications

摘要

Biodegradable multi-blocked polyurethane (PU) based micelles with a hydrophilic PEG corona were extensively studied for anti-cancer drug delivery systems. The hydrophilic PEG segment usually incorporated as a soft segment or as an end capping reagent, which has difficulty forming a dense PEG coating with a brush like conformation due to the low mobility of the PEG domains at the soft segment and the low amount of the PEG at the end of PU chains. In the present study, biodegradable pH sensitive polyurethane micelles with a dense brush like coating of PEG were prepared by a new kind of PEG grafted polyurethanes (PEG- g -PU) which were synthesized using PEGylated diethanolamine (MPEG-DEAM) as a chain extender. The high mobility of pendant MPEG in PEG- g -PU results in the formation of a dense and brush like PEG corona on the PEG- g -PU micelles. Meanwhile the MPEG attached on the hard segment will transfer the diethanolamine (DEAM) to the surface of nanoparticles during the self-assembly process and the DEAM render the particles with positive charges which potentially enhances cellular uptake and endosomal escape. DLS, TEM and AFM showed that a dense PEG domain was formed on the surface of PEG- g -PU micelles while no obvious PEG microdomain was observed for the other two kinds of micelles. FTIR and DSC results demonstrated the enhanced microphase separation of PEG- g -PU micelles compared with PEG- g -PU bulk materials and the other two contrast PU micelles, i.e. PEG- b -PU and PEG- c -PU. Paclitaxel (PTX) was chosen as a model hydrophobic drug to evaluate the loading and pH-triggered release of the PU micelles. The enhanced cytotoxicity of PTX-loaded PEG- g -PU-3 micelles against H460 cancer cells reveals that they are more potent for intracellular delivery of PTX as compared to PEG- b -PU-3 and PEG- c -PU-3 micelles.