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咪康唑或氟康唑的纳米载体:对三种生物膜的影响及体外细胞毒性作用

Nanocarriers of Miconazole or Fluconazole: Effects on Three-Species Biofilms and Cytotoxic Effects In Vitro.

作者信息

Caldeirão Anne Caroline Morais, Araujo Heitor Ceolin, Arias Laís Salomão, Ramírez Carmona Wilmer, Miranda Gustavo Porangaba, Oliveira Sandra Helena Penha, Pessan Juliano Pelim, Monteiro Douglas Roberto

机构信息

Graduate Program in Dentistry, University of Western São Paulo (UNOESTE), Presidente Prudente 19050-920, SP, Brazil.

Department of Preventive and Restorative Dentistry, School of Dentistry, São Paulo State University (Unesp), Araçatuba 16015-050, SP, Brazil.

出版信息

J Fungi (Basel). 2021 Jun 23;7(7):500. doi: 10.3390/jof7070500.

Abstract

The contribution of different species in oral fungal infections has stimulated the search for more effective therapies. This study assessed the antibiofilm effects of nanocarriers of miconazole (MCZ) or fluconazole (FLZ) on biofilms, and their cytotoxic effects on murine fibroblasts. Three-species biofilms () were formed on 96-well plates, and they were treated with nanocarriers (iron oxide nanoparticles coated with chitosan-"IONPs-CS") of MCZ or FLZ at 39/78/156 µg/mL; antifungals alone at 156 µg/mL and artificial saliva were tested as positive and negative controls, respectively. Biofilms were analyzed by colony forming units (CFU), biomass, metabolic activity, and structure/viability. The cytotoxicity (L929 cells) of all treatments was determined via 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay. Data were submitted to one- or two-way ANOVA, followed by Tukey's or Fisher LSD's tests ( < 0.05). IONPs-CS-MCZ at 78 µg/mL promoted similar antibiofilm and cytotoxic effects compared with MCZ at 156 µg/mL. In turn, IONPs-CS-FLZ at 156 µg/mL was overall the most effective FLZ antibiofilm treatment, surpassing the effects of FLZ alone; this nanocarrier was also less cytotoxic compared with FLZ alone. It can be concluded that both nanocarriers are more effective alternatives to fight biofilms compared with their respective positive controls in vitro, being a promising alternative for the treatment of oral fungal infections.

摘要

不同物种在口腔真菌感染中的作用促使人们寻找更有效的治疗方法。本研究评估了咪康唑(MCZ)或氟康唑(FLZ)纳米载体对生物膜的抗生物膜作用及其对小鼠成纤维细胞的细胞毒性作用。在96孔板上形成三种物种的生物膜,并用浓度为39/78/156μg/mL的MCZ或FLZ纳米载体(壳聚糖包被的氧化铁纳米颗粒-“IONPs-CS”)进行处理;分别以156μg/mL的单一抗真菌剂和人工唾液作为阳性和阴性对照进行测试。通过菌落形成单位(CFU)、生物量、代谢活性和结构/活力对生物膜进行分析。通过3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐(MTT)还原试验测定所有处理的细胞毒性(L929细胞)。数据进行单因素或双因素方差分析,随后进行Tukey检验或Fisher LSD检验(P<0.05)。与156μg/mL的MCZ相比,78μg/mL的IONPs-CS-MCZ具有相似的抗生物膜和细胞毒性作用。反过来,156μg/mL的IONPs-CS-FLZ总体上是最有效的FLZ抗生物膜治疗方法,超过了单一FLZ的效果;与单一FLZ相比,这种纳米载体的细胞毒性也更小。可以得出结论,与各自的阳性对照相比,两种纳米载体在体外对抗生物膜更有效,是治疗口腔真菌感染的一种有前景的替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb4d/8305882/e0affb1a5545/jof-07-00500-g001.jpg

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