Efficient delivery systems are fundamental to the clinical translation of mRNA-based therapeutics and vaccines. Poly(β-amino ester) (pBAE) nanocarriers represent a versatile platform for mRNA delivery, as their chemical composition and architecture can be tuned to control encapsulation efficiency and structural stability. Crucially, the protonation state of pBAE polymers is highly pH-dependent, which directly influences the electrostatic interactions with the negatively charged mRNA and, consequently, the complexation dynamics. While initial complexation is initiated at a lower formulation pH (5.2) driven by strong cationic charges, evaluating the stability of these nanoparticles at physiological pH (7.4) is fundamental to accurately model their transport and structural integrity within a bloodstream-like environment, where protecting the genetic cargo from enzymatic degradation is critical.