Department of Pharmaceutics, College of Pharmaceutical Sciences, Southwest University , Chongqing , People's Republic of China.
Drug Deliv. 2015;22(5):627-37. doi: 10.3109/10717544.2014.880756. Epub 2014 Jan 29.
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.
The present study was aimed at evaluating the concurrent use of two antibiotics, daptomycin and clarithromycin, against methicillin-resistant Staphylococcus aureus (MRSA) infections.
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.
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.
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.
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.
病原体的进化速度目前超过了新药物的开发速度，由于新抗生素的开发悬而未决，因此联合使用现有药物进行治疗可能是一种有效的替代治疗方法。
本研究旨在评估两种抗生素（达托霉素和克拉霉素）联合使用治疗耐甲氧西林金黄色葡萄球菌（MRSA）感染的效果。
采用聚乙二醇（PEG）化脂质体（载有达托霉素、克拉霉素或两者的混合物（PL[CD]），以优化的质量比 1:32 进行负载，并通过动态光散射和电子显微镜进行了表征。采用体外和体内方法比较了脂质体对 MRSA 的作用。
PL[CD]稳定，平均（±SD）囊泡直径为 98.2±2.21nm，包封效率分别为 94.71±1.37%（达托霉素）和 92.94±1.21%（克拉霉素）。与仅载有达托霉素的脂质体相比，PL[CD]在体外表现出明显增强的抗 MRSA 活性，显著降低了 MRSA 细菌负荷，并提高了宿主的存活率。
达托霉素与克拉霉素联合载药在仅含达托霉素脂质体所需浓度的三十分之一时就产生了显著的抗 MRSA 活性。
这些发现表明，达托霉素和克拉霉素的联合脂质体递送具有成为治疗 MRSA 感染的有效且毒性更小的治疗方法的潜力。
