Bismuth-thiol incorporation enhances biological activities of liposomal tobramycin against bacterial biofilm and quorum sensing molecules production by Pseudomonas aeruginosa

被引:53
作者
Halwani, Majed [1 ]
Hebert, Stephanie [1 ]
Suntres, Zacharias E. [1 ,3 ]
Lafrenie, Robert M. [2 ,5 ]
Azghani, Ali O. [4 ]
Omri, Abdelwahab [1 ]
机构
[1] Laurentian Univ, Dept Chem & Biochem, Novel Drug & Vaccine Delivery Syst Facil, Sudbury, ON P3E 2C6, Canada
[2] No Ontario Sch Med, Div Med Sci, Sudbury, ON P3E 2C6, Canada
[3] No Ontario Sch Med, Div Med Sci, Thunder Bay, ON P7B 5E1, Canada
[4] Univ Texas Tyler, Dept Biol, Tyler, TX 75799 USA
[5] NE Ontario Reg Canc Ctr, Div Tumour Biol, Sudbury, ON P3E 5J1, Canada
关键词
Liposomes; Tobramycin; Bismuth; Cystic fibrosis; Quorum sensing; Sputum; CYSTIC-FIBROSIS SPUTUM; IN-VITRO; PULMONARY RETENTION; RESISTANCE; RELEASE; INFECTIONS; STAPHYLOCOCCI; EXPRESSION; VIRULENCE; TOXICITY;
D O I
10.1016/j.ijpharm.2009.02.001
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Recurrent pulmonary infection and inflammation are major risk factors for high morbidity and mortality in patients with cystic fibrosis (CF). As such, frequent antibiotic use and drug resistant bacterial strains are main concerns in individuals with CF. Bacterial virulence and resistance are influenced by unique CF airways fluid lining and Pseudomonas aeruginosa quorum sensing (QS) and biofilm formation. We have developed a novel liposome formulation consist of bismuth-thiol and tobramycin (LipoBiEDT-TOB) that is non-toxic and highly effective against planktonic bacteria. In this study, we examined the effect of LipoBiEDT-TOB on QS molecule N-acyl homoserine lactone (AHL) secretion by P. aeruginosa isolates in the presence of Agrobacterium tumefaciens reporter strain (A136). LipoBiEDT-TOB activity against biofilm forming P. aeruginosa was compared to free tobramycin using the Calgary Biofilm Device (CBD). Our data indicate that LipoBiEDT-TOB prevents AHL production at low tobramycin concentration (as low as 0.012 mg/l) and stops biofilm forming P aeruginosa growth at 64 mg/l. The formulation is stable in different biological environments (biofilm, sputum, and bronchoalveolar lavage) and is able to penetrate CF sputum. Taken together, co-encapsulation of bismuth-thiol metal with tobramycin in liposome improves its antimicrobial activities in vitro. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:141 / 146
页数:6
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