4.5 Article

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

Journal

ACS INFECTIOUS DISEASES
Volume 8, Issue 10, Pages 2059-2072

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.2c00017

Keywords

erythrocyte liposomes; antibiotics; targeted drug delivery; polymyxin B encapsulation and delivery; antibody anchoring; antibiotic specificity

Funding

  1. Natural Sciences and Engineering Research Council of Canada (NSERC)
  2. Canada Foundation for Innovation (CFI)
  3. Ontario Ministry of Economic Development and Innovation
  4. Canada Graduate Scholarship-Master's (CGS-M)
  5. Province of Ontario
  6. University Scholar of McMaster University

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Due to the worldwide antibiotic resistance crisis, many existing antibiotics have become ineffective. Researchers have developed a novel PmB delivery system using hybrid erythrocyte liposomes and antibacterial antibodies, which can deliver antibiotics to specific targets efficiently.
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 (RBCcm). Anti-Escherichia coli 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 similar to 90% and are effective in delivering PmB to E. coli, with values for the minimum inhibitory concentration (MIC) being comparable to those of free PmB. The MIC values for Klebsiella aerogenes, however, significantly increased well beyond the resistant breakpoint, indicating that the inclusion of the anti-E. coli antibodies enables the erythro-PmBs to selectively deliver antibiotics to specific targets.

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