Synthesis of oligo(ethylene glycol)-modified hyperbranched poly(glycidol)s for dual sensitization of liposomes to pH and temperature

Abstract

A new type of polymers that change characters responding to pH and temperature was synthesized by modifying biocompatible hyperbranched poly(glycidol) (HPG) with temperature-sensitive oligo(ethylene glycol)s and pH-sensitive succinyl groups. HPG with the average polymerization degree of 40 was reacted with excess succinic anhydride and then, succinylated HPG was reacted with methoxy tri(ethylene glycol), ethoxy tri(ethylene glycol) (ETEG) or their mixtures, which afforded HPGs having oligo(ethylene glycol) and succinyl groups with varying compositions. These HPG derivatives dissolved in aqueous solutions exhibited a cloud point at a specific temperature, above which these polymers became water-insoluble. Their cloud points decreased with decreasing pH, indicating that these polymers have pH- and temperature-responsive properties. Liposomes were prepared by hydrating mixtures of egg yolk phosphatidylcholine and anchor-conjugated HPG derivatives with aqueous pyranine solution. These polymer-modified liposomes were destabilized and released pyranine under weakly acidic and mildly high temperature conditions. In addition, temperature and pH regions where the liposome destabilization was induced were affected by the polymer compositions such as succinyl groups and oligo(ethylene glycol) contents. Considering biocompatible structure and dual stimuli-responding properties, the HPG derivatives might be potential usefulness for the production of functional liposomes that achieve site-specific intracellular drug delivery in combination with local hyperthermia.