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Galleria mellonella for systemic assessment of anti-Candida auris using amphotericin B loaded in nanoemulsion
Science of the Total Environment ( IF 8.2 ) Pub Date : 2021-10-16 , DOI: 10.1016/j.scitotenv.2021.151023
Gabriel Davi Marena 1 , Matheus Aparecido Dos Santos Ramos 1 , Laura Caminitti Lima 2 , Marlus Chorilli 1 , Tais Maria Bauab 2
Affiliation  

Galleria mellonella is a model that uses adult larvae to assess the prophylactic, therapeutic, and acute toxic potential of substances. Given their benefits, G. mellonella models are being employed in investigations of systemic infections caused by highly resistant microorganisms. Among the multiresistant microorganisms, we highlight Candida auris, a yeast with high mortality potential and resistance. Among the potential drugs, amphotericin B (AmB) stands out; however, microbial resistance episodes and side effects caused by low selectivity have been observed. The incorporation of AmB into a nanoemulsion (NE) can contribute to the control of C. auris infections and resistance as well as decrease the side effects of this drug. This study aimed to develop AmB-loaded NE (NEA) and evaluate its antifungal action against C. auris in G. mellonella. NEs were obtained by using sunflower oil and cholesterol as the oily phase, polyoxyethylene 20 cetyl ether (Brij® 58) and soy phosphatidylcholine as the surfactant system, and PBS buffer as the aqueous phase. An alternative in vivo assay with G. mellonella for acute toxicity and infection was performed using adult stage larvae (200 mg to 400 mg). According to the obtained results, NE and NEA exhibited sizes of 43 and 48 nm, respectively. The PDI was 0.285 and 0.389 for NE and NEA, respectively. The ZP showed electronegativity for both systems, with −3.77 mV and −3.80 mV for NE and NEA, respectively. Acute toxicity showed that free AmB had greater acute toxicity potential than NEA. The survival assay showed high larval viability. NEA had a better antifungal profile against systemic infection in G. mellonella. It is concluded that the alternative model proved to be an efficient in vivo assay to determine the toxicity and evaluate the therapeutic property of free AmB and NEA in systemic infections caused by C. auris.



中文翻译:

Galleria mellonella 使用纳米乳中负载的两性霉素 B 对抗耳念珠菌进行系统评估

Galleria mellonella是一种模型,它使用成虫幼虫来评估物质的预防、治疗和急性毒性潜力。鉴于它们的好处,大蜡螟模型正被用于研究由高度耐药微生物引起的全身感染。在多重抗性微生物中,我们重点介绍了耳念珠菌,这是一种具有高死亡率和耐药性的酵母。在潜在的药物中,两性霉素B(AmB)脱颖而出;然而,已经观察到由低选择性引起的微生物耐药性事件和副作用。将 AmB 掺入纳米乳剂 (NE) 有助于控制耳念珠菌感染和抵抗力以及减少这种药物的副作用。本研究旨在开发AMB-NE加载(NEA),并评价其抗真菌作用对C.耳。通过使用向日葵油和胆固醇作为油相、聚氧乙烯 20 鲸蜡基醚 (Brij® 58) 和大豆磷脂酰胆碱作为表面活性剂体系以及 PBS 缓冲液作为水相获得 NE。G. mellonella的另一种体内测定使用成虫期幼虫(200 毫克至 400 毫克)进行急性毒性和感染的试验。根据获得的结果,NE 和 NEA 的尺寸分别为 43 和 48 nm。NE 和 NEA 的 PDI 分别为 0.285 和 0.389。ZP 对两个系统都显示出电负性,NE 和 NEA 分别为 -3.77 mV 和 -3.80 mV。急性毒性表明游离 AmB 比 NEA 具有更大的急性毒性潜力。存活试验显示幼虫存活率高。NEA 对G. mellonella 的全身感染具有更好的抗真菌特性。得出的结论是,替代模型被证明是一种有效的体内试验,用于确定毒性和评估游离 AmB 和 NEA 在由念珠菌引起的全身感染中的治疗特性.

更新日期:2021-10-17
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