Nano-polyplexes from a cationic modification of poly(γ-glutamic acid)

In this study, a cationic biopolymer has been developed through the chemical modification of a biodegradable and biocompatible polymer such as poly(γ-glutamic acid) (PGGAH). A series of PGGAH_xTMEA_y copolymers with varying degrees of cationic groups incorporation (11-95%) were synthesized by partial esterification of carboxylate side groups of PGGAH with 2-bromoethyl trimethylammonium bromide (BrETABr). The copolymers were thoroughly characterized using ¹H NMR, FTIR, TGA, and GPC analyses. It was found that the degree of esterification had a pronounced effect on the thermal stability, and DNA-binding capacity of the copolymers. Higher degrees of modification were shown to enhance the excellent potential for DNA complexation, forming polyplex nanoaggregates with sizes in the range of 80-220 nm at various ammonium-to-phosphate (N/P) ratios. The stability, size, and surface charge of these polyplexes were monitored over two weeks in aqueous solutions using dynamic light scattering (DLS). Enhanced stability in polyplex formation was exhibited by copolymers with higher degrees of modification, which maintained consistent particle sizes across different N/P ratios. This study provides valuable insights into the development of efficient DNA delivery systems based on a new cationically modified poly(γ-glutamic acid) derivative.