Aims: To explore the role of modifying the phospholipid composition of liposomal nanoparticles (LNPs) on their uptake. Methods: Different LNPs were labeled with a fluorescent marker and their uptake by human lung fibroblast (WI-38) cells was evaluated using flow cytometry and confocal microscopy. Linezolid was loaded in LNPs showing enhanced uptake, and their ability to reduce intracellular methicillin-resistant Staphylococcus aureus (MRSA) was investigated by in vitro infection. Results: Liposomes with disaturated dipalmitoylphosphatidylcholine–phosphatidylglycerol–phosphatidylethanolamine at a molar ratio of 60:10:10, mimicking that of WI-38 cells, were more effectively uptaken. Linezolid-loaded LNPs significantly reduced intracellular MRSA viable count. Conclusion: Modified LNPs could be promising antibiotic nanocarriers for targeting intracellular MRSA, which are usually resistant to conventional antibiotics.

Plain language summary

Liposomal nanoparticles (LNPs) are considered effective drug-delivery nanocarriers. We investigated the effect of altering the phospholipid composition of LNPs on their uptake into lung cells. Intracellular uptake of LNPs with different phospholipids was evaluated. LNPs showing enhanced uptake were loaded with linezolid antibiotic and their potential to kill the intracellular bacteria was explored as the difficulty for an antibiotic to reach the intracellular bacteria results in treatment failure. LNPs with phospholipid composition similar to that of the lung cells were effectively uptaken and were also able to deliver linezolid into lung cells and kill the intracellular bacteria. This approach could be successfully applied to reduce the antibiotic dose and subsequently overcome antibiotic resistance.

Tweetable abstract

Liposomal nanocarriers with phospholipids mimicking that of lung cells could be an attractive approach in potentiating cellular uptake and reducing the viable count of intracellular methicillin-resistant Staphylococcus aureus.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 18, No. 6

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History

Received 20 March 2022

Accepted 15 February 2023

Published online 11 May 2023

Published in print April 2023

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Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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