(149b) Buffering Effects on the Solution Behavior and Hydrolytic Degradation of Poly(?-amino ester)s

Poly(b-amino ester)s (PBAEs), cationic polymers originally developed as gene therapy vectors, have found their way into increasingly diverse applications, owing to their simple and efficient synthesis, facile incorporation of a variety of functional groups, and highly tunable hydrolytic degradation. The protonation of tertiary amines on each repeat unit along the backbone yields pH-responsive solution properties and degradation profiles, as well as a high buffering capacity. However, the opposing effects of pH on PBAE solubility and hydrolysis have led to conflicting reports of acidic conditions accelerating degradation in some cases and slowing degradation in others. Therefore, to unify understanding of PBAE degradation and solution properties, we studied PBAE hydrolysis as a function of pH and buffer concentration. We observed that, at high buffer concentrations, well above the molar concentration of PBAE amines, the solution pH remains constant throughout the degradation process. In these high buffer concentration conditions, increasing pH accelerated hydrolytic degradation. Yet, it is common to employ PBAE-based materials in 1X phosphate-buffered saline (PBS) to mimic physiological solutions, and 1X PBS contains just 10 mM phosphate buffer. When the concentration of PBAE amines exceeds that of buffer, the polymer and its hydrolytic degradation essentially control solution pH. Regardless of the original pH of a 10 mM buffer, dissolution of 20 mg/mL PBAE (corresponding to 60 mM amines) afforded a solution pH of 8, which decreased as PBAE hydrolysis evolved acid. These studies showcase the role of buffering on the pH-dependent degradation and solution properties of PBAEs, providing guidance for programming degradation of these polymers for applications ranging from drug delivery to thermosets.