Biomimetic amphiphilic chitosan nanoparticles: Synthesis, characterization and antimicrobial activity

Naturally derived antimicrobial peptides (AMPs) are an attractive source of new antimicrobial agents. However, clinical application of AMPs is associated with poor bioavailability and toxicity. In this study, we address these limitations by designing a new series of chitosan derivatives to mimic the amphiphilic topology of AMPs. The synthesized chitosan derivatives were found to self-assemble into nanoparticles in the aqueous environment. Among the compounds, a chitosan derivative grafted with arginine and oleic acid (CH-Arg-OA) exhibited the most potent antimicrobial activity, especially against Gram-negative bacteria. It also caused minimal cell death when tested in HEK293 and HepG2 cell lines, thus confirming the role of cationicity and lipophilicity for selective bacteria targeting. CH-Arg-OA exhibited its antimicrobial activity by disrupting bacterial membranes and causing the leakage of cytoplasmic contents. Thus, amphiphilic chitosan nanoparticles offer a great promise as a new class of AMPs mimics that is effective against Gram-negative bacteria.