Rukholm Gavin, Mugabe Clement, Azghani Ali O, Omri Abdelwahab
The Novel Drug and Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, Ont., Canada P3E 2C6.
Int J Antimicrob Agents. 2006 Mar;27(3):247-52. doi: 10.1016/j.ijantimicag.2005.10.021. Epub 2006 Feb 10.
Cystic fibrosis (CF) is a common and lethal genetic disorder with a carrier frequency of 1 in 29 Caucasians. Chronic respiratory infections with Pseudomonas aeruginosa are the leading cause of morbidity and mortality in individuals with CF. Aminoglycoside antibiotics, including gentamicin, are highly effective against P. aeruginosa, but severe toxicity limits their use. One potential strategy for avoiding this problem is to encapsulate aminoglycosides in liposomes. In this study, we compared the bactericidal capacity of liposome-encapsulated gentamicin with that of free antibiotic against clinical isolates of P. aeruginosa. Liposome size, encapsulation efficiency and minimal inhibitory concentrations (MICs) of the free and liposomal gentamicin against gentamicin-sensitive and -resistant strains of P. aeruginosa were determined. In vitro time-kill studies were performed using free and liposomal gentamicin at 1, 2 or 4 times the MICs. The average liposomal size was 426.25 +/- 13.56 nm, with a gentamicin encapsulation efficiency of 4.51 +/- 0.54%. The MICs for liposomal gentamicin were significantly lower than those of corresponding free gentamicin. In addition, the time-kill values for liposomal gentamicin were either equivalent to or better than those of the free antibiotic. In conclusion, our liposomal gentamicin formulation is a more potent antipseudomonal drug with an improved killing time and prolonged antimicrobial activity.
囊性纤维化（CF）是一种常见的致死性遗传病，在白种人中携带者频率为1/29。铜绿假单胞菌引起的慢性呼吸道感染是CF患者发病和死亡的主要原因。包括庆大霉素在内的氨基糖苷类抗生素对铜绿假单胞菌高效，但严重的毒性限制了它们的使用。避免这个问题的一个潜在策略是将氨基糖苷类药物包裹在脂质体中。在本研究中，我们比较了脂质体包裹的庆大霉素与游离抗生素对铜绿假单胞菌临床分离株的杀菌能力。测定了脂质体大小、包封效率以及游离和脂质体庆大霉素对铜绿假单胞菌敏感和耐药菌株的最低抑菌浓度（MIC）。使用游离和脂质体庆大霉素，在MIC的1、2或4倍浓度下进行体外时间杀菌研究。脂质体平均大小为426.25 +/- 13.56 nm，庆大霉素包封效率为4.51 +/- 0.54%。脂质体庆大霉素的MIC显著低于相应的游离庆大霉素。此外，脂质体庆大霉素的时间杀菌值与游离抗生素相当或更好。总之，我们的脂质体庆大霉素制剂是一种更有效的抗假单胞菌药物，具有改善的杀菌时间和延长的抗菌活性。
