The role of hydrophobic alkyl chains in the physicochemical properties of poly(β-amino ester)/DNA complexes

Two degradable poly(β-amino ester)s with an average molecular weight of 2. kDa, referred to as B1 and B2, have been synthesized to be tested as non-viral gene delivery systems. B2 polymer exhibits two additional non-polar ethyl groups at both ends. This paper describes the influence of that subtle difference on the compaction ability and temporal stability of the complexes formed with plasmid DNA. Our results suggest that the inclusion of those small hydrophobic fragments into the polycation backbone improves its suitability as synthetic DNA carrier. The improvement is related to the formation and physicochemical properties of the complexes. B2 polyplexes were more stable, the polymer hydrolysis was slowed down and plasmid DNA was better protected which was translated into better transfection efficiencies. Although still not totally understood, the role played by hydrophobic forces is ubiquitous in chemical, biological and physical systems, and they must be considered to design future polymers for gene delivery.