Antimicrobial peptide-modified pH-sensitive micelles against pneumonia caused by methicillin-resistant Staphylococcus aureus

Bacterial infections in the lungs can cause severe illness and pose a heavy economic burden. Antibiotics are the first clinical choice to combat bacterial infections, but most of them lack selective targeting on the infection site, which limits the antibacterial effect of these antibiotics. Increasing the antibiotic concentration in infected tissues is necessary to eradicate the pathogenic bacteria, and nano-micelle delivery systems hold great promise in solving this problem. To attain controlled drug release at the infection site and target therapy to the infected lung, we used a pH-sensitive membrane, PEG114-PDPA10, and modified the antimicrobial peptide Magainin II (MagII) on the micellar surface. MagII-modified micelles of azithromycin (AZI) and luteolin (Lut) with pH sensitivity (MagII-AZI/Lut-Ms) were constructed. MagII-AZI/Lut-Ms had higher drug release in vitro at a low pH for the same period. The in vitro antibacterial mechanism results revealed that MagII-AZI/Lut-Ms targeted methicillin-resistant S. aureus (MRSA) and had higher antibacterial activity than the other groups. According to the results of in vivo fluorescence experiments, MagII-AZI/Lut-Ms improved the targeting of micelles and increased the drug concentration at the infection site. The in vivo antibacterial results also revealed that MagIIAZI/Lut-Ms had a better therapeutic effect on the mice with MRSA-induced pneumonia. These results indicate that MagII-AZI/Lut-Ms is expected to be used safely for the treatment of pneumonia caused by MRSA.