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Erythro-PmBs: A Selective Polymyxin B Delivery System Using Antibody-Conjugated Hybrid Erythrocyte Liposomes
Hannah Krivić1,2, Sebastian Himbert1,2, Ruthie Sun1,2
1Department of Physics and Astronomy, McMaster University, HamiltonL8S 4M1, Ontario, Canada.
Abstract:
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-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 ∼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.
Insights
This study introduces a novel drug delivery system using red blood cell liposomes to improve polymyxin B (PmB) delivery. The system shows high efficiency and targeted delivery, offering a promising approach to combat antibiotic resistance.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Antimicrobial Resistance
Background:
- Antibiotic resistance is a global health crisis, rendering many existing treatments ineffective.
- Polymyxin B (PmB) is a potent antibiotic but limited by toxicity, often reserved as a last resort.
- Novel delivery systems are needed to enhance antibiotic efficacy and reduce side effects.
Purpose of the Study:
- To develop a novel drug delivery system for polymyxin B (PmB) using hybrid erythrocyte liposomes conjugated with antibodies.
- To enhance PmB retention and achieve targeted delivery to specific bacterial pathogens.
- To evaluate the efficacy and specificity of the developed erythrocyte-liposome-PmB system.
Main Methods:
- Constructed hybrid erythrocyte liposomes by incorporating negatively charged lipids for enhanced PmB retention.
- Conjugated anti-Escherichia coli antibodies to the liposomes using DSPE-PEG maleimide linkers for targeted delivery.
- Assessed PmB loading efficiency and determined minimum inhibitory concentration (MIC) values against bacterial strains.
Main Results:
- The novel erythrocyte liposome system achieved a high PmB loading efficiency of approximately 90%.
- Erythro-PmBs demonstrated effective delivery of PmB to Escherichia coli, with MIC values comparable to free PmB.
- A significant increase in MIC values for Klebsiella aerogenes indicated selective targeting by the anti-E. coli antibodies.
Conclusions:
- The developed hybrid erythrocyte liposomes offer an efficient and targeted delivery system for polymyxin B.
- Antibody conjugation enables selective delivery of PmB, enhancing its efficacy against specific bacterial targets like E. coli.
- This approach holds potential for overcoming challenges associated with antibiotic resistance and toxicity.
