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Arianna J. Partow,Miju Kim,Peixin Fan,Ting Liu,Zhaohui Tong,Kwangcheol C. Jeong 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.113 No.-
The safety of using nano-emulsion drug delivery systems is a growing concern. Here, we conducted riskassessments of an innovative combination therapy for multidrug resistant pathogens by encapsulatingcephalosporin antibiotics and b-lactamase inhibitors with chitosan nanoparticles (CNAIs) using in vitrohuman cell lines and an in vivo animal model, Caenorhabditis elegans. The four combinations of CNAIsincluding two cephalosporin antibiotics (cefotaxime and ceftiofur) with two b-lactamase inhibitors (tazobactamand clavulanate) were engineered as water–oil-water emulsions. CNAIs maintained stableantimicrobial activity in various thermal challenges. CNAIs exerted strong antimicrobial activity butdid not cause toxicity in human cell lines measured by cell membrane integrity, mitochondria activity,and reactive oxygen species generation. Reported damage was observed at 8 lg/mL and 16 lg/mL foronly two of the four combinations of CNAIs. More importantly, CNAIs at 4 lg/mL did not cause adverseeffects on the lifespan of C. elegans. In summary, CNAIs do not cause toxicity at working concentrationin vitro and in vivo risk assessments, suggesting that nano-emulsion drug delivery systems can be anew framework for developing treatments for multidrug pathogen infections.