pH‐Dependent Structural Changes in Polyethyleneimine and its implications

Amine functional polyelectrolytes are widely used for non-viral gene delivery, apart from various other industrial applications. Amongst these polyethyleneimine, PEI, a gold standard, has been extensively investigated to understand its pH-based protonation dynamics.  Very recent studies have revealed that at low pH PEI undergoes self-assembled micron-sized fibrillar structures. This can have huge implications on PEI-based gene-therapy. In our work, we explore the molecular behaviour of PEI upon protonation with various acids to uncover the mechanisms driving this self-assembly. Our results show that it arises primarily from counter-ion condensation on the protonated amine groups and hydrophobic interactions between PEI chains. Notably, a pH and polarity gradient emerges between the surface and core, leading to a slow, inward-propagating protonation front over several days. This gradual protonation induces a curvature change, driving the morphological transition into anisotropic structures that further self-assemble into micron-sized hollow fibres.These insights offer valuable implications for the rational design of advanced PEI-based gene delivery systems.

(1)        Sharma, S.; Mishra, M.; Srivatsav, A. T.; Sharma, K. P.; Kapoor, S. pH-Dependent Structural Changes in Polyethyleneimine Affect Its Gene Transfection Efficiency. Small n/a (n/a), 2411293. https://doi.org/10.1002/smll.202411293.