Milo Scarlet, Hathaway Hollie, Nzakizwanayo Jonathan, Alves Diana R, Esteban Patricia Pérez, Jones Brian V, Jenkins A Toby A
Department of Chemistry, University of Bath, BA2 7AY, UK.
J Mater Chem B. 2017 Jul 21;5(27):5403-5411. doi: 10.1039/c7tb01302g. Epub 2017 Jun 27.
The crystalline biofilms of Proteus mirabilis can seriously complicate the care of patients undergoing long-term indwelling urinary catheterisation. Expression of bacterial urease causes a significant increase in urinary pH, leading to the supersaturation and precipitation of struvite and apatite crystals. These crystals become lodged within the biofilm, resulting in the blockage of urine flow through the catheter. Here, we describe an infection-responsive surface coating for urinary catheters, which releases a therapeutic dose of bacteriophage in response to elevated urinary pH, in order to delay catheter blockage. The coating employs a dual-layered system comprising of a lower hydrogel 'reservoir' layer impregnated with bacteriophage, capped by a 'trigger' layer of the pH-responsive polymer poly(methyl methacrylate-co-methacrylic acid) (EUDRAGIT®S 100). Evaluation of prototype coatings using a clinically reflective in vitro bladder model system showed that catheter blockage time was doubled (13 h to 26 h (P < 0.05)) under conditions of established infection (10 CFU ml) in response to a 'burst-release' of bacteriophage (10 PFU ml). Coatings were stable both in the absence of infection, and in the presence of urease-negative bacteria. Quantitative and visual analysis of crystalline biofilm reduction show that bacteriophage constitute a promising strategy for the prevention of catheter blockage, a clinical problem for which there is currently no effective control method.
奇异变形杆菌的结晶生物膜会严重使长期留置导尿管患者的护理复杂化。细菌脲酶的表达会导致尿液pH值显著升高,从而导致鸟粪石和磷灰石晶体过饱和并沉淀。这些晶体滞留在生物膜内,导致尿液无法通过导管流出。在此,我们描述了一种用于导尿管的感染响应性表面涂层,该涂层在尿液pH值升高时释放治疗剂量的噬菌体,以延缓导管堵塞。该涂层采用双层系统,包括浸渍有噬菌体的下层水凝胶“储存器”层,上面覆盖有pH响应性聚合物聚(甲基丙烯酸甲酯-共-甲基丙烯酸)(Eudragit®S 100)的“触发”层。使用临床反映性体外膀胱模型系统对原型涂层进行评估表明,在已建立感染(10 CFU/ml)的情况下,由于噬菌体“爆发释放”(10 PFU/ml),导管堵塞时间翻倍(从13小时增加到26小时(P < 0.05))。涂层在无感染以及存在脲酶阴性细菌的情况下均稳定。对结晶生物膜减少的定量和视觉分析表明,噬菌体是预防导管堵塞的一种有前景的策略,而导管堵塞是目前尚无有效控制方法的临床问题。
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