Abstract
Purpose :
To evaluate betainized polyethyleneimine (B-PEI) zwitterions as a novel approach to treat corneal pathogens. We hypothesize that the relative positive surface properties exhibited by most pathogens can be utilized by B-PEI-based zwitterion compounds to shield and neutralize infectious contact and potentially mitigate ocular infection.
Methods :
This in vitro study was conducted with the University of South Florida Eye Institute and collaborators at the Tulane University Department of Microbiology. Testing was performed on B-PEI, B-PEI Hydrochloric acid (B-PEI HCl), B-PEI boric acid (B-PEI BA), B-PEI citric acid (B-PEI CA), and the controls gentamicin, fluconazole, and deionized water. The pathogen groups included S. Aureus, E. Coli, P. Aeruginosa, C. Albicans, and SARS-CoV-2 (COVID-19). Pathogen-to-drug contact time was 30 minutes for all samples and delivery concentrations were 100% for all compounds. The main outcomes were the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum fungicidal concentration (MFC), and viral log reduction value (LRV).
Results :
The S. Aureus sample groups had an MIC of 0.009 mg/mL (Gentamicin), 2.5 mg/mL (B-PEI HCl, B-PEI BA), 5 mg/mL (B-PEI), 10 mg/mL (B-PEI CA) and an MBC of 5 mg/mL (B-PEI BA), 10 mg/mL (B-PEI HCl), and 20 mg/mL (B-PEI, B-PEI CA). E. Coli had an MIC of 0.0019 mg/mL (Gentamicin), 2.5 mg/mL (B-PEI HCl, B-PEI BA), 5 mg/mL (B-PEI CA) and an MBC of 10 mg/mL (B-PEI HCl, B-PEI BA) and 20 mg/mL (B-PEI, B-PEI CA). P. aeruginosa was found to have an MIC of 0.0039 mg/mL (Gentamicin), 2.5 mg/mL (B-PEI HCl), 5 mg/mL (B-PEI, B-PEI BA), 10 mg/mL (B-PEI CA) and an MBC of 5 mg/mL (B-PEI HCl), 10 mg/mL (B-PEI BA), and 20 mg/mL (B-PEI, B-PEI CA). C. Albicans had an MIC of 0.005 mg/mL (Fluconazole), 2.5 mg/mL (B-PEI HCl), 5 mg/mL (B-PEI BA), 10 mg/mL (B-PEI, B-PEI CA) and an MBC of 5 mg/mL (B-PEI HCl), 10 mg/mL (B-PEI BA), and 20 mg/mL (B-PEI, B-PEI CA). SARS-CoV-2 had a LRV of 1.6 (B-PEI HCl, B-PEI CA), 1.0 (B-PEI), and 0 (B-PEI BA, deionized water).
Conclusions :
Our results indicate that compared to the standard treatments, B-PEI derivatives require a much high delivery dose. Among the B-PEI derivatives B-PEI HCl had the most potent bactericidal, fungicidal, and viricidal properties. Future in vivo studies are needed to evaluate the pan-microbial impact of B-PEI derived compounds on corneal ulcers and infectious biofilm.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.