Intracellular delivery of antibiotics to methicillin-resistant Staphylococcus aureus (MRSA) – infected macrophages and keratinocytes

Methicillin-resistant Staphylococcus aureus (MRSA) can invade and survive in mammalian host cells, causing persistent and recurrent infections. Although vancomycin and gentamicin are potent against active extracellular MRSA, they are not effective against intracellular MRSA due to the low cellular uptake of the antimicrobials. Therefore, alternative antimicrobial approaches are being researched upon to eliminate these intracellular bacteria. One strategy is the use of delivery systems to carry these drugs directly to the target cells. Here, we propose a non-toxic lipid-polymer hybrid nanoparticle (LPN) system composed of a solid polymer core (i.e. PLGA; poly lactic-co-glycolic acid) and a cationic lipid shell (i.e. DOTAP) for localized, sustained release of antimicrobial agents to intracellular bacteria. LPNs were synthesized through a simple and robust self-assembly approach. Encapsulated gentamicin and vancomycin were more effective in eliminating intracellular MRSA compared to the free formulations. Cellular uptake of LPN was seen in both keratinocytes and macrophages, where the uptake level was higher in macrophages than that in keratinocytes. The novel formulations of this LPN system could be a useful method to enhance the efficiency of antimicrobial agents to eliminate intracellular bacteria.