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A Milk Extracellular Vesicle-Based Nanoplatform Enhances Combination Therapy Against Multidrug-Resistant Bacterial
Shaoqi Qu1, Shuo Yang1, Qingjun Xu1
1Animal-Derived Food Safety Innovation Team, College of Veterinary Medicine, Anhui Agricultural University, Hefei, 230036, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 25, 2024
Summary
New functionalized milk extracellular vesicles loaded with polymyxin and plumbagin effectively combat multidrug-resistant bacteria. This biomimetic delivery system enhances oral administration and shows promise for treating severe bacterial infections.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Antimicrobial Research
Background:
- Rising prevalence of multidrug-resistant (MDR) bacterial infections necessitates novel therapeutic strategies.
- Limited antibiotic discovery pipeline highlights the need for innovative approaches, including antibiotic adjuvants and improved delivery systems.
Purpose of the Study:
- To develop a biomimetic delivery system for enhanced oral administration of combination antibacterial therapy.
- To identify compounds that potentiate the efficacy of existing antibiotics against MDR bacteria.
Main Methods:
- Established a screening platform using a polymyxin-resistant strain to identify effective adjuvants, leading to the selection of plumbagin.
- Engineered functionalized milk extracellular vesicles (FMEVs) to co-load polymyxin and plumbagin.
- Investigated drug mechanisms, including membrane damage and metabolic disruption.
- Evaluated FMEV transcellular transport via citric acid-mediated tight junction opening.
- Assessed therapeutic efficacy in a murine model of MDR Escherichia coli peritonitis-sepsis.
Main Results:
- FMEVs co-loaded with polymyxin and plumbagin eradicated 99% of bacteria within 4 hours in vitro.
- The combination therapy demonstrated synergistic effects by damaging bacterial membranes and disrupting energy metabolism.
- FMEVs exhibited efficient transcellular transport, enhancing drug delivery.
- Significant efficacy was observed in a mouse model of peritonitis-sepsis caused by MDR E. coli.
Conclusions:
- Functionalized milk extracellular vesicles represent a promising biomimetic platform for oral delivery of combination antibacterial therapies.
- This approach effectively enhances the efficacy of polymyxin by combining it with plumbagin and improving its delivery.
- The strategy offers a potential solution to combat challenging multidrug-resistant bacterial infections.
