The Novel Drug & Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, P3E 2C6, Canada.
J Antimicrob Chemother. 2010 Apr;65(4):684-93. doi: 10.1093/jac/dkq036. Epub 2010 Feb 15.
This study examined the activities of tobramycin and bismuth against quorum sensing, virulence factors and biofilms of Pseudomonas aeruginosa by co-encapsulating the agents in liposomes in order to achieve greater delivery of the agents.
The inhibitory effects of the agents, in either their conventional (free) or vesicle-entrapped (liposomal) formulations, were assessed by measuring the changes in the quorum-sensing signal molecule N-acyl homoserine lactone, pyoverdine, pyocyanin, elastase, protease, chitinase, bacterial attachment and biofilms in vitro.
The effectiveness of tobramycin and bismuth was superior when they were co-administered as a liposomal formulation as measured by their ability to attenuate the production of N-acyl homoserine lactone, elastase (P < 0.01), protease (P < 0.05) and chitinase (P < 0.01). In the presence of non-lethal concentrations of free and liposomal tobramycin and bismuth, bacterial attachment was attenuated. Biofilm formation was also attenuated with free tobramycin and bismuth, yet, in the presence of liposomal tobramycin and bismuth, biofilm complexes could form but contained mostly dead bacteria. When established biofilms were treated with higher concentrations, free tobramycin and bismuth killed and detached bacteria, while the liposomal tobramycin and bismuth penetrated and killed bacteria in the cores of the biofilms.
These data suggest that treatment of P. aeruginosa with tobramycin and bismuth, as measured by the changes in quorum sensing, virulence factors and biofilms, is most effective when delivered as a liposomal formulation at a lower concentration compared with the free formulation.
本研究通过将药物共同包封在脂质体中以实现更大的药物递送，从而考察妥布霉素和铋对抗铜绿假单胞菌群体感应、毒力因子和生物膜的活性。
通过测量群体感应信号分子 N-酰基高丝氨酸内酯、绿脓菌素、吡咯烷酮、弹性蛋白酶、蛋白酶、几丁质酶、细菌附着和生物膜的变化，评估药物（无论是常规（游离）还是囊泡包封（脂质体）制剂）的抑制作用。
妥布霉素和铋联合使用脂质体制剂时效果更好，其表现为能够减弱 N-酰基高丝氨酸内酯、弹性蛋白酶（P<0.01）、蛋白酶（P<0.05）和几丁质酶（P<0.01）的产生。在非致死浓度的游离和脂质体妥布霉素和铋存在的情况下，细菌附着被减弱。游离妥布霉素和铋也能减弱生物膜的形成，但在存在脂质体妥布霉素和铋的情况下，生物膜复合物可以形成，但主要包含死亡细菌。当用更高浓度处理已建立的生物膜时，游离妥布霉素和铋杀死并脱离细菌，而脂质体妥布霉素和铋则穿透并杀死生物膜核心中的细菌。
这些数据表明，与游离制剂相比，以脂质体形式、更低浓度给药时，通过群体感应、毒力因子和生物膜的变化来衡量，妥布霉素和铋治疗铜绿假单胞菌的效果最佳。
