JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Liposomal co-delivery of daptomycin and clarithromycin at an optimized ratio for treatment of methicillin-resistant Staphylococcus aureus infection.

CONTEXT: Pathogen evolution currently outpaces novel drug development, and because development of new antibiotics is pending, combination therapy with existing drugs may provide effective alternative treatments.

OBJECTIVE: The present study was aimed at evaluating the concurrent use of two antibiotics, daptomycin and clarithromycin, against methicillin-resistant Staphylococcus aureus (MRSA) infections.

MATERIALS AND METHODS: Polyeythylene glycol (PEGylated liposomes loaded with daptomycin, clarithromycin, or both (PL[CD]) at an optimized mass ratio of 1:32 were generated and characterized using dynamic light scattering and electron microscopy. In vitro and in vivo approaches were used to compare liposome effects on MRSA.

RESULTS: PL[CD] were stable, with a mean (± SD) vesicle diameter of 98.2 ± 2.21 nm and encapsulation efficiency of 94.71 ± 1.37% (daptomycin) and 92.94 ± 1.21% (clarithromycin). Compared with daptomycin-only liposomes, PL[CD] showed significantly enhanced anti-MRSA activity in vitro and significantly reduced MRSA bacterial load and increased host survival in vivo.

DISCUSSION: Co-delivery of daptomycin with clarithromycin produced significant anti-MRSA activity in the presence of only one-thirtieth of the concentration required in liposomes containing daptomycin only.

CONCLUSION: These findings suggested that concurrent liposomal delivery of daptomycin and clarithromycin has the potential to be an effective and less toxic treatment for MRSA infections.

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