Staphylococcus aureus–directed liposome for targeted chemotherapy against infection—evaluation of affinity and antibacterial activity

Staphylococcus aureus is a bacterium well known to cause respiratory infections. Recently, drug delivery via inhalation has garnered attention as a potential route of antibiotic administration owing to its ability to minimize systemic side effects. Liposomal antibiotics can enhance the local drug concentration in the lungs, enable controlled release, and improve biofilm penetration, thereby enhancing efficacy and reducing side effects. However, administration of conventional liposomal formulations for inhalation leads to nonspecific distribution outside the infection site. Accordingly, we developed S. aureus–targeted liposomes with CARG peptides, capable of selectively binding S. aureus, present on the liposome surface. Liposomal surface modification with the CARG peptide via a polyethylene glycol (PEG) spacer selectively increased the affinity toward S. aureus, specifically a 1.6-fold enhanced binding with S. aureus, whereas no such increased binding was observed with Pseudomonas aeruginosa under suspension-culture conditions. Furthermore, CARG liposomes efficiently permeated biofilms owing to the presence of PEG and demonstrated high affinity for S. aureus in biofilms. The antimicrobial activity of CARG liposomes tended to be enhanced when applied to rifampicin-loaded liposomes. These results suggest that the modification of the CARG peptide on the liposomal surface can enhance the targeting ability of S. aureus and its antimicrobial activity.

Graphical Abstract