Halwani Majed, Hebert Stéphanie, Suntres Zacharias E, Lafrenie Robert M, Azghani Ali O, Omri Abdelwahab
The Novel Drug & Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, P3E 2C6, Canada.
Int J Pharm. 2009 May 21;373(1-2):141-6. doi: 10.1016/j.ijpharm.2009.02.001. Epub 2009 Feb 12.
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.
反复肺部感染和炎症是囊性纤维化（CF）患者高发病率和高死亡率的主要危险因素。因此，频繁使用抗生素和耐药菌株是CF患者的主要担忧。细菌的毒力和耐药性受CF气道独特的液体衬里以及铜绿假单胞菌群体感应（QS）和生物膜形成的影响。我们开发了一种由铋硫醇和妥布霉素组成的新型脂质体制剂（LipoBiEDT-TOB），它对浮游细菌无毒且高效。在本研究中，我们在根癌农杆菌报告菌株（A136）存在的情况下，检测了LipoBiEDT-TOB对铜绿假单胞菌分离株分泌QS分子N-酰基高丝氨酸内酯（AHL）的影响。使用卡尔加里生物膜装置（CBD），将LipoBiEDT-TOB对形成生物膜的铜绿假单胞菌的活性与游离妥布霉素进行了比较。我们的数据表明，LipoBiEDT-TOB在低妥布霉素浓度（低至0.012 mg/l）时可阻止AHL产生，并在64 mg/l时抑制形成生物膜的铜绿假单胞菌生长。该制剂在不同生物环境（生物膜、痰液和支气管肺泡灌洗液）中稳定，并且能够穿透CF痰液。综上所述，在脂质体中将铋硫醇金属与妥布霉素共包封可提高其体外抗菌活性。
