Tunable Phase-Separation Behavior of Thermoresponsive Polyampholytes Through Molecular Design

Here, we report that carboxylated poly-l-lysine, a polyampholyte, shows lower critical solution temperature (LCST)-type temperature-responsive liquid-liquid phase separation and coacervate formation in aqueous solutions. The phase-separation temperature of polyampholytes is strongly affected by the polymer concentration, balance between the carboxyl and amino groups, hydrophobicity of the side chain, and NaCl concentration in the solution. We concluded that the phase separation was caused by both electrostatic interactions between the carboxyl and amino groups and intermolecular hydrophobic interactions. The addition of NaCl weakened the electrostatic interactions, causing the two phases to remix. The introduction of the hydrophobic moiety decreased the phase-separation temperature by making the molecular interactions stronger. Finally, temperature-responsive hydrogels were prepared from the polyampholytes to explore their applicability as biomaterials and in drug delivery systems. The fine-tuning of the phase-separation temperature of poly-l-lysine-based polyampholytes through molecular design should open new avenues for their use in precisely controlled biomedical applications. (c) 2016 Wiley Periodicals, Inc.