Amino Acid-Based Biodegradable Polycations with Antimicrobial Activity

摘要

The bactericidal activity of arginine-based polycations-polyesterurethane (PEUR- EG_2-Arg-EG_4) and polyesterureas (PEU-1-Arg-2 and 1-Arg-3) toward the bacteria: Bacillus subtilis, Staphilococcus aureus, Mycobacterium album, Pseudomonas fluorescens, Esherichia coli was studied in in vitro experiments. Biodegradable polycations - polyesterurethane (PEUR - EG_2-Arg-EG_4) and polyesterureas (PEU - 1-Arg-2 and 1-Arg-3) were synthesized on the base of bis-nucleophilic monomers - bis-(oamino acid)α,ω-alkylene diesters and bis-electrophilic monomers: activated bis-carbonates and activated diol-bis-carbonates by the method of low-temperature polycondensation in solution. The key monomers for the synthesis of arginine-containing polymers -bis-(α-amino acid)α,ω-alkylene diesters contain two, easily hydrolizable ester bonds and are stable in the form of salts of di-p-toluene sulfonic acid. The arginine-based polymers were studied according to the standard methods. Their yield was satisfactory, and reduced viscosity varied in the range of 0.1-0.2dl/g (M_w~ 8-10KDa). The bactericidal activity of polycations was studied using the Photocolorimetric method. It was estimated that the studied polycations reveal bactericidal activity which depends on their chemical structure. Correlation between hydrophobicity level of polycations and their bactericidal activity was established. The bactericidal activity of polycations was exposed mainly in logarithmic phase of bacterial development. New arginine-containing polymers reveal significantly lower cytotoxicity towards the eucariotic cells than the polycations widely spread in genetic ingineering. The arginine-containing biodegradable polycations with hydrophobic fragments are able to form micro- and nanoparticles, which makes them very attractive as bactericidal preparations of a new generation and physiologicaly active containers for purposeful drug delivery systems.