Transformation of Cytotoxic Linear Polyethyleneimine (L‐ <scp>PEI</scp> ) Into Biocompatible and Hemacompatible Crosslinked Particles With Antimicrobial Properties

ABSTRACT Linear polyethyleneimine (L‐PEI) microgel/particles were prepared using glycerol diglycidyl ether (GDE) as crosslinker at various mole ratios, 10%, 25%, and 50% of L‐PEI repeating unit, and designated as L‐PEI‐1, L‐PEI‐2, and L‐PEI‐3, respectively. All microgels were found blood compatible with &lt; 2% hemolysis and &gt; 80% blood clotting indexes at 1000 μg/mL concentrations, whereas L‐PEI is hemolytic (&gt; 80% hemolysis). Similarly, L‐PEI showed cytotoxicity on L929 fibroblasts even at 50 μg/mL, while &gt; 80% cell viability was observed for L‐PEI‐based particles even at 1000 μg/mL. Although it is regarded as less cytotoxic than branched PEI, the cross‐linked L‐PEI particles effectively circumvent cytotoxicity as the most important limitation of L‐PEI in biological applications. Additionally, the higher antimicrobial activity against Escherichia coli , gram‐negative bacteria, Bacillus subtilis , gram‐positive bacteria strains, and Candida albicans , yeast strains was observed for L‐PEI‐1 and protonated L‐PEI‐1 particles. Moreover, the antibacterial activity of L‐PEI‐1 particles was further improved after the inclusion of Ag(I) and Cu(II) ions within L‐PEI particles as Ag@L‐PEI‐1 and Cu@L‐PEI‐1 composites, respectively. The lower MIC and MBC values were determined for Ag@L‐PEI‐1 particles against Escherichia coli and Bacillus subtilis as 0.079 and 0.312 mg/mL, respectively, and an MFC value for Candida albicans was 0.156 mg/mL for Ag@L‐PEI‐1 particles.