Erythro-PmBs: A selective polymyxin B delivery system using antibody-conjugated hybrid erythrocyte liposomes

The growing world-wide antibiotic resistance crisis has caused many currently existing antibiotics to become ineffective due to bacteria developing resistive mechanisms. There are a limited number of potent antibiotics that are successful at suppressing microbial growth; however, these are often deemed as a last resort due to toxicity. We present a novel PmB delivery system constructed by conjugating hybrid erythrocyte liposomes with antibacterial antibodies to combine a high loading efficiency with guided delivery. PmB retention is enhanced through incorporation of the negatively charged lipid, DMPS, into the red blood cell’s cytoplasmic membrane¹. Molecular dynamics (MD) simulations reveal an optimal DMPS fraction that allows for complete anchorage of PmB through acyl tail insertion into the hydrophobic membrane core. Anti-Escherichia coli antibodies are attached to these hybrid erythrocyte liposomes by inclusion of DSPE-PEG maleimide linkers. We show that these erythro-PmBs have a loading efficiency of ~90% and are effective in delivering PmB to E.coli, with values for the minimum inhibitory concentration (MIC) comparable to those of free PmB. MD simulations further suggest a fusion or lipid exchange mechanism between the erythro-PmBs and outer E.coli membrane. The MIC values for Klebsiella aerogenes, however, significantly increased, indicating that anti-E.coli antibody inclusion enables the erythro-PmBs to selectively deliver antibiotics to specific targets.