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Enhanced clearing of Candida biofilms on a 3D urothelial cell in vitro model using lysozyme-functionalized fluconazole-loaded shellac nanoparticles
Biomaterials Science ( IF 6.6 ) Pub Date : 2021-09-16 , DOI: 10.1039/d1bm01035b
Anheng Wang 1 , Paul J Weldrick 1 , Leigh A Madden 2 , Vesselin N Paunov 3
Affiliation  

Candida urinary tract biofilms are increasingly witnessed in nosocomial infections due to reduced immunity of patients and the hospital ecosystem. The indwelling devices utilized to support patients with urethral diseases that connect the unsterilized external environment with the internal environment of the patient are another significant source of urinary tract biofilm infections. Recently, nanoparticle (NP)-associated therapeutics have gained traction in a number of areas, including fighting antibiotic-resistant bacterial biofilm infection. However, most studies on nanotherapeutic delivery have only been carried out in laboratory settings rather than in clinical trials due to the lack of precise in vitro and in vivo models for testing their efficiency. Here we develop a novel biofilm-infected 3D human urothelial cell culture model to test the efficiency of nanoparticle (NP)-based antifungal therapeutics. The NPs were designed based on shellac cores, loaded with fluconazole and coated with the cationic enzyme lysozyme. Our formulation of 0.2 wt% lysozyme-coated 0.02 wt% fluconazole-loaded 0.2 wt% shellac NPs, sterically stabilised by 0.25 wt% poloxamer 407, showed an enhanced efficiency in removing Candida albicans biofilms formed on 3D layer of urothelial cell clusteroids. The NP formulation exhibited low toxicity to urothelial cells. This study provides a reliable in vitro model for Candida urinary tract biofilm infections, which could potentially replace animal models in the testing of such antifungal nanotechnologies. The reproducibility and availability of a well-defined biofilm-infected 3D urothelial cell culture model give valuable insights into the formation and clearing of fungal biofilms and could accelerate the clinical use of antifungal nanotherapeutics.

中文翻译:

使用溶菌酶功能化的氟康唑负载虫胶纳米颗粒增强 3D 尿路上皮细胞体外模型上念珠菌生物膜的清除

由于患者和医院生态系统的免疫力下降,念珠菌尿路生物膜越来越多地出现在医院感染中。用于支持尿道疾病患者的留置装置将未消毒的外部环境与患者的内部环境连接起来,是尿道生物膜感染的另一个重要来源。最近,纳米颗粒 (NP) 相关疗法在许多领域受到关注,包括对抗抗生素耐药性细菌生物膜感染。然而,由于缺乏精确的体外体内研究,大多数关于纳米治疗递送的研究仅在实验室环境中进行,而不是在临床试验中进行用于测试其效率的模型。在这里,我们开发了一种新型生物膜感染 3D 人类尿路上皮细胞培养模型,以测试基于纳米颗粒 (NP) 的抗真菌疗法的效率。NPs 是基于虫胶核设计的,负载氟康唑并涂有阳离子溶菌酶。我们的 0.2 wt% 溶菌酶包被 0.02 wt% 氟康唑负载 0.2 wt% 虫胶纳米颗粒的配方,由 0.25 wt% 泊洛沙姆 407 空间稳定,在去除尿路上皮细胞簇的 3D 层上形成的白色念珠菌生物膜方面表现出更高的效率。NP 制剂对尿路上皮细胞表现出低毒性。本研究为念珠菌提供了可靠的体外模型泌尿道生物膜感染,在这种抗真菌纳米技术的测试中,它有可能取代动物模型。明确定义的生物膜感染 3D 尿路上皮细胞培养模型的可重复性和可用性为真菌生物膜的形成和清除提供了宝贵的见解,并可以加速抗真菌纳米治疗药物的临床应用。
更新日期:2021-09-16
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