Erythro-PmBs: A Selective Polymyxin B Delivery System Using Antibody-Conjugated Hybrid Erythrocyte Liposomes

As a result of the growing worldwide antibiotic resistance crisis, many currently existing antibiotics have become ineffective due to bacteria developing resistive mechanisms. There are a limited number of potent antibiotics that are successful at suppressing microbial growth, such as polymyxin B (PmB); however, these are often deemed as a last resort due to their 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. The retention of PmB is enhanced by incorporating negatively charged lipids into the red blood cells' cytoplasmic membrane (RBC). Anti- antibodies are attached to these hybrid erythrocyte liposomes by the 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 , with values for the minimum inhibitory concentration (MIC) being comparable to those of free PmB. The MIC values for , however, significantly increased well beyond the resistant breakpoint, indicating that the inclusion of the anti- antibodies enables the erythro-PmBs to selectively deliver antibiotics to specific targets.