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

As a result of the growing world-wide antibiotic resistance crisis, many currently existing antibiotics have become ineffective due to bacteria developing resistive mechanisms. There are a limited number of potent antibiotics successful at suppressing microbial growth, such as polymyxin B (PmB); however, they are deemed as a last resort due to their toxicity. We present a novel PmB delivery system constructed by conjugating hybrid erythrocyte liposomes with bacterial antibodies to combine a high loading efficiency with guided delivery. PmB encapsulation is enhanced by incorporating negatively charged lipids into the red blood cells' cytoplasmic membrane. Anti-E.coli antibodies are attached to the hybrid erythrocyte liposomes through DSPE-PEG malemeide 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. MIC values for K. aerogenes were significantly increased beyond the resistant breakpoint, indicating that inclusion of the  anti-E.coli antibodies enables the Erythro-PmBs to selectively deliver antibiotics to specific targets. This versatile platform can be used for different types of antibiotics and bacterial targets.