pH-dependent hemolysis of biocompatible imidazole-grafted polyaspartamide derivatives

A series of novel, pH-sensitive, endosomolytic polymers based on imidazole-grafted polyaspartamide were synthesized to characterize the pH-sensitive membrane fusion properties of red blood cells and their toxicity to L929 cells. All imidazole-containing polymers exhibited strong cationic characteristics under acidic conditions, as well as a high buffering effect in the pH range 5-7. In the presence of O-(2-aminoethyl)-O'-methylpolyethylene glycol and 1-(3-aminopropyl)imidazole-grafted polyaspartamide (MPEG/API-g-PASPAM) systems red blood cells agglutinated below pH 6.5 without any hemolytic effect. The octadecylamine, O-(2-aminoethyl)-O'-methylpolyethylene glycol and 1-(3-aminopropyl)imidazole-grafted polyaspartamide (C18/MPEG/API-g-PASPAM) systems, however, displayed considerable hemolytic behavior below pH 6.5, but no hemolysis occurred above this pH. It can be concluded from these results that not only the pH-sensitive imidazole group, but also the hydrophobic octadecyl chain plays a critical role in membrane fusion. The hypothetical mechanism of this fusion involves both ionic and hydrophobic interactions between the polymers and lipid bilayers. (C) 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.