The cold supply chain for vaccines represents a substantial portion of vaccine distribution’s cost and logistical challenges. Notably, nearly half of vaccines are compromised due to temperature regulation failures. Such challenges significantly impede relief operations’ ability to preserve vaccine efficacy. Developing vaccines and other thermolabile therapeutics that withstand higher temperature thresholds is imperative to alleviate the dependency on cold storage. Current scientific discourse increasingly concentrates on encapsulation methods such as complex coacervation to achieve this objective. Our research investigates polyelectrolyte complexation composed of a lysine-based peptide or peptoid and a nucleic acid, assessing the impact of chirality on the complexation and phase separation with nucleic acids. We explored homochiral and racemic peptides and achiral peptoids with three different nucleic acids, dsDNA, ssDNA, and tRNA, to determine the type of phase separation, salt stability, and thermal stability of our materials. Though many groups focus on complex coacervation, a liquid-liquid phase separation, we evaluated both coacervation and precipitation as we see these solid complexes as an analog to lyophilization. Our studies reveal that the chirality of the polymers and the presence of salt play significant roles in the morphology of complexes and the degree of phase separation. We conducted stability assessments for temperature via circular dichroism and ionic strength through salt curves. The insights gleaned from our research are poised to significantly inform the development of drug delivery formulations and, therefore, have the potential to enhance the accessibility of vaccines.
