Cationic polymers have been extensively investigated
as a potential
replacement for traditional antibiotics. Here, we examined the effect
of molecular weight (MW) on the antimicrobial, cytotoxic, and hemolytic
activity of linear polytrimethylenimine (L-PTMI). The results indicate
that the biological activity of the polymer sharply increases as MW
increases. Thanks to a different position of the antibacterial activity
and toxicity thresholds, tuning the MW of PTMI allows one to achieve
a therapeutic window between antimicrobial activity and toxicity concentrations.
L-PTMI presents significantly higher antimicrobial activity against
model microorganisms than linear polyethylenimine (L-PEI) when polymers
with a similar number of repeating units are compared. For the derivatives
of L-PTMI and L-PEI, obtained throughN-monomethylation
and partialN,N-dimethylation of linear polyamines,
the antimicrobial activity and toxicity were both reduced; however,
resulting selectivity indices were higher. Selected materials were
tested against clinical isolates of pathogens from the ESKAPE group
andMycobacteria, revealing good antibacterial properties
of L-PTMI against antibiotic-resistant strains of Gram-positive and
Gram-negative bacteria but limited antibacterial properties againstMycobacteria.